Rayna J Gonzales

Interests

Research

Cardiovascular disease and stroke; Neuro-degenerative, developmental and psychiatric disease; Cardiac and vascular biology; Signaling and steroid biology

Courses

Scholarly Contributions

Journals/Publications

• Wendt, T. S., & Gonzales, R. J. (2023). Ozanimod Differentially Preserves Human Cerebrovascular Endothelial Barrier Proteins and Attenuates MMP-9 Activity Following In Vitro Acute Ischemic Injury. American Journal of Physiology: Cell Physiology.
• Wendt, T. S., & Gonzales, R. J. (2023). Ozanimod Attenuates Human Cerebrovascular Endothelial Derived MMP-9 Activity and Preserves Barrier Properties Following In Vitro Acute Ischemic Injury. Bio-archive (planned submission to Function in 2023).
• Wendt, T. S., Li, Y. J., & Gonzales, R. J. (2021). Ozanimod, an S1PR1 ligand, attenuates hypoxia plus glucose deprivation-induced autophagic flux and phenotypic switching in human brain VSM cells.. American Journal of Physiology. Cell Physiology, 320(6), C1055-C1073. doi:10.1152/ajpcell.00044.2021
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  Vascular smooth muscle (VSM) cell phenotypic expression and autophagic state are dynamic responses to stress. Vascular pathologies, such as hypoxemia and ischemic injury, induce a synthetic VSM phenotype and autophagic flux resulting in a loss of vascular integrity and VSM cell death respectfully. Both clinical pilot and experimental stroke studies demonstrate that sphingosine-1-phosphate receptor (S1PR) modulation improves stroke outcome; however, specific mechanisms associated with a beneficial outcome at the level of the cerebrovasculature have not been clearly elucidated. We hypothesized that ozanimod, a selective S1PR type 1 ligand, will attenuate VSM synthetic phenotypic expression and autophagic flux in primary human brain VSM cells following acute hypoxia plus glucose deprivation (HGD; in vitro ischemic-like injury) exposure. Cells were treated with ozanimod and exposed to normoxia or HGD. Crystal violet staining, standard immunoblotting, and immunocytochemical labeling techniques assessed cellular morphology, vacuolization, phenotype, and autophagic state. We observed that HGD temporally decreased VSM cell viability and concomitantly increased vacuolization, both of which ozanimod reversed. HGD induced a simultaneous elevation and reduction in levels of pro- and antiautophagic proteins respectfully, and ozanimod attenuated this response. Protein levels of VSM phenotypic biomarkers, smoothelin and SM22, were decreased following HGD. Furthermore, we observed an HGD-induced epithelioid and synthetic morphological appearance accompanied by disorganized cytoskeletal filaments, which was rescued by ozanimod. Thus, we conclude that ozanimod, a selective S1PR1 ligand, protects against acute HGD-induced phenotypic switching and promotes cell survival, in part, by attenuating HGD-induced autophagic flux thus improving vascular patency in response to acute ischemia-like injury.
• Li, Y. J., Shi, S. X., Liu, Q., Shi, F. D., & Gonzales, R. J. (2020). Targeted role for sphingosine-1-phosphate receptor 1 in cerebrovascular integrity and inflammation during acute ischemic stroke. Neuroscience letters, 735, 135160.
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  Endothelial sphingosine-1-phosphate receptors are emerging as relevant therapeutic targets during acute ischemic stroke (AIS). Physiologically, the cerebrovascular endothelium plays a vital role in maintaining barrier integrity and cerebrovascular homeostasis. During a cerebral ischemic event, products from parenchymal cell death are released and trigger vascular endothelial dysfunction and vascular inflammation leading to barrier integrity disruption. Endothelial dysfunction, inflammation, and a breach in barrier property play a significant role in contributing to a vicious cycle which promotes brain edema formation and exacerbates neuronal injury post stroke. Data from experimental stroke models and clinical trials suggest that selective sphingosine-1-phosphate receptor type 1 (S1PR1) modulation improves endothelial health and function and, as a result, contributes to improved neurological outcome post ischemic injury. This review highlights the impact of sphingosine-1-phosphate (S1P)/S1PR1 signaling involved in blood brain barrier (BBB) integrity and cerebrovascular inflammation following AIS. We focus on the beneficial actions of S1PR1 signaling during ischemic injury including barrier protection to lessen brain edema formation and reduction in the development and progression of vascular inflammation by attenuating endothelial cell activation resulting in reduced neurovascular inflammation. Potential gaps and future directions related to the role of S1PR during AIS are also discussed.
• Shi, S., Rodriguez, J., Gonzales, R. J., & Beer, Y. (2020). 3β‐Diol Attenuates COX‐2 Levels in a Neonatal In‐Vivo and In‐Vitro Ischemic Injury Rodent and Human Model. The FASEB Journal, 34(S1), 1-1. doi:10.1096/fasebj.2020.34.s1.09808
• Wendt, T. S., Li, Y. J., Gonzales, R. J., & Albrecht, A. G. (2020). Ozanimod Protects Against Hypoxia plus Glucose Deprivation‐Induced Morphological Changes and Improves Cell Health in Human Brain Vascular Smooth Muscle. The FASEB Journal, 34(S1), 1-1. doi:10.1096/fasebj.2020.34.s1.08725
• Wendt, T. S., Shi, F., Liu, Q., Li, Y. J., & Gonzales, R. J. (2020). Ozanimod Attenuates Ischemia‐Induced Inflammation and Dysfunction in Human Brain Microvascular Endothelial Cells. The FASEB Journal, 34(S1), 1-1. doi:10.1096/fasebj.2020.34.s1.08694
• Gonzales, R. J., AC, D., CS, F., JC, O., KR, S., CR, B., TM, H., SS, A., CC, C., & JM, D. (2019). Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle-specific manner. Physiological Reports.
• Li, H., Zhou, X., Yu Jing, L., Gonzales, R. J., S, Q., Shi, F., & Liu, Q. (2019). The selective sphingosine 1-phosphate receptor 1 modulator, RP101075 improves cerebrovascular dynamics in microvascular thrombosis. FASEB J..
• Raman, P., & Gonzales, R. J. (2019). Saturated fatty acids induce inflammation in blood vessels. Medicine Innovates.
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  Saturated fatty acids induce inflammation in blood vessels. Gonzales, RJ and Puneet Raman, Medicine Innovates 2018
• Shi, S., Shi, F. D., Liu, Q., Li, Y., & Gonzales, R. J. (2019). Selective Sphingosine‐1‐Phosphate Receptor‐1 Ligand Protects Against Ischemia‐Induced Inflammation and Dysfunction in Human Brain Microvascular Endothelial Cells. The FASEB Journal, 33(S1). doi:10.1096/fasebj.2019.33.1_supplement.677.10
• Jin, W. N., Ducruet, A. F., Liu, Q., Shi, S. X., Waters, M., Zou, M., Sheth, K. N., Gonzales, R., & Shi, F. D. (2018). Activation of JAK/STAT3 restores NK-cell function and improves immune defense after brain ischemia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 32(5), 2757-2767.
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  Stroke-induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/or producing cytokines such as IFN-γ. Because the phenotype and function of peripheral NK cells have been widely investigated in ischemic stroke, nCounter Inflammation Gene Array Analysis was used to build immune-related gene profiles of NK cells to comprehensively analyze the molecular signature of NK cells after ischemic brain injury. We observed distinct gene expression profiles reflecting different splenic NK-cell phenotypes and functional properties across the time course of transient middle cerebral artery occlusion (MCAO). Based on gene expression and pathway-network analysis, lower expression levels of signal transducer and activator of transcription-3 (STAT3) were observed in animals with MCAO compared with sham control animals. Genetic activation of STAT3 through the introduction of STAT3 clustered regularly interspaced short palindromic repeats (CRISPR) plasmid prevented the loss of NK-cell-derived IFN-γ production after MCAO, together with reduced bacterial burden and mortality. Our data suggest that brain ischemia impairs NK-cell-mediated immune defense in the periphery, at least in part through the JAK-STAT3 pathway, which can be readdressed by modulating STAT3 activation status.-Jin, W.-N., Ducruet, A. F., Liu, Q., Shi, S. X.-Y., Waters, M., Zou, M., Sheth, K. N., Gonzales, R., Shi, F.-D. Activation of JAK/STAT3 restores NK-cell function and improves immune defense after brain ischemia.
• Jin, W. N., Gonzales, R., Feng, Y., Wood, K., Chai, Z., Dong, J. F., La Cava, A., Shi, F. D., & Liu, Q. (2018). Brain Ischemia Induces Diversified Neuroantigen-Specific T-Cell Responses That Exacerbate Brain Injury. Stroke, 49(6), 1471-1478.
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  Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury.
• Raman, P., Madhavpeddi, L., & Gonzales, R. J. (2018). Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells. American journal of physiology. Cell physiology, 314(5), C545-C553.
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  Vascular basal cyclooxygenase-2 (COX-2) expression and activity can be induced by endotoxin, hypoxia, or ischemia. During vascular pathologies such as atherosclerosis, increases in COX-2 activity result in prostanoid production, a contributor to the development and progression of vascular inflammation leading to unstable atherosclerotic plaques and increased risk for thrombotic events. Recent studies demonstrate that select free fatty acids, such as palmitate, can act as proinflammatory mediators. However, the effect of palmitate on COX-2 expression and activity, and its impact on the development and progression of vascular inflammation, are not well elucidated. We investigated the effect of palmitate on COX-2 expression and function in human vascular smooth muscle cells. Cells were treated with palmitate, COX-2 protein levels were assessed using Western analysis, and activity was assessed via ELISA. We observed that palmitate dose-dependently increased COX-2 levels and specifically enhanced band intensity of the COX-2 74 kDa band (slowest migrating band). This response was attenuated by N-linked glycosylation inhibition, suggesting that palmitate impacts expression of the fully activated glycoform of COX-2. Palmitate-induced increases in COX-2 levels correlated with an increase in prostaglandin E production that was also attenuated by a glycosylation inhibitor. Additionally, palmitate altered cell morphology and increased cell density which were reversed by selective COX-2 inhibition. Thus, we conclude that palmitate acts on COX-2 by two separate mechanisms of action in human vascular smooth muscle. It elicits dose-dependent increases in COX-2 protein expression and modulates regulation of COX-2 activity via modification of posttranslational glycosylation.
• Tian, D. C., Shi, K., Zhu, Z., Yao, J., Yang, X., Su, L., Zhang, S., Zhang, M., Gonzales, R. J., Liu, Q., Huang, D., Waters, M. F., Sheth, K. N., Ducruet, A. F., Fu, Y., Lou, M., & Shi, F. D. (2018). Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow. Annals of neurology, 84(5), 717-728.
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  The present study was undertaken to determine the efficacy of coadministration of fingolimod with alteplase in acute ischemic stroke patients in a delayed time window.
• Awwad, I., D'Lugos, A. C., Carroll, C. C., Gonzales, R. J., Sweazea, K. L., Dickinson, J. M., Angadi, S. S., & Hale, T. (2017). Exercise Preconditioning as A Means To Protect The Kidney Against Doxorubicin-Induced Oxidative Stress. Experimental Biology.
• Dickinson, J. M., D'Lugos, A. C., Mahmood, T. N., Ormsby, J. C., Salvo, L., Dedmon, W. L., Patel, S. H., Katsma, M. S., Mookadam, F., Gonzales, R. J., Hale, T. M., Carroll, C. C., & Angadi, S. S. (2017). Exercise Protects Skeletal Muscle during Chronic Doxorubicin Administration. Medicine and science in sports and exercise, 49(12), 2394-2403.
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  This study aimed to assess the ability for exercise training performed before and during biweekly doxorubicin (DOX) administration to attenuate adverse effects of DOX on skeletal muscle. We hypothesized that DOX treatment would increase REDD1, impair mammalian target of rapamycin (mTOR) signaling, and reduce muscle fiber size, and that exercise training would attenuate these responses.
• Jin, W. N., Shi, S., Wood, K., Gonzales, R. J., & Liu, Q. (2017). Depletion of microglia exacerbates post ischemic inflammation and brain injury. Journal of Cerebral Blood Flow and Metabolism.
• Li, H. D., Li, M., Shi, E., Jin, W. N., Wood, K., Gonzales, R., & Liu, Q. (2017). A translocator protein 18 kDa agonist protects against cerebral ischemia/reperfusion injury. Journal of neuroinflammation, 14(1), 151.
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  Cerebral ischemia is a leading cause of death and disability with limited treatment options. Although inflammatory and immune responses participate in ischemic brain injury, the molecular regulators of neuroinflammation after ischemia remain to be defined. Translocator protein 18 kDa (TSPO) mainly localized to the mitochondrial outer membrane is predominantly expressed in glia within the central nervous system during inflammatory conditions. This study investigated the effect of a TSPO agonist, etifoxine, on neuroinflammation and brain injury after ischemia/reperfusion.
• Liu, Q., & Gonzales, R. J. (2017). Targeting mitogen-activated protein kinase in acute ischemic stroke. Acta Physiologica, doi: 10.1111/apha.12848 [Epub ahead of print].
• Liu, Q., Jin, W. N., Liu, Y., Shi, K., Sun, H., Zhang, F., Zhang, C., Gonzales, R. J., La Cava, A., & Shi, F. (2017). Brain ischemia suppresses natural killer cell- mediated immunity after stroke. Immunity.
• Hale, T. M., Mahmood, T. N., Jarrett, C. L., Hale, T. M., Gonzales, R. J., Dickinson, J. M., D'lugos, A. C., Carroll, C. C., & Angadi, S. S. (2016). Effect of High Intensity Exercise Preconditioning and Training on Antioxidant Enzymes in Cardiomyocytes During Doxorubicin Treatment. The FASEB Journal, 30.
• Raman, P., & Gonzales, R. J. (2015). Palmitate-Induced Glycosylation of Cyclooxygenase-2 in Primary Human Vascular Smooth Muscle Cells. The FASEB Journal, 29.
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  Obesity is a major risk factor for cardiovascular health and function. One possible cause of obesity is poor nutrition, including the consumption of diets high in saturated fatty acids. Since vascu...
• Rodriguez, P., Patel, S. I., & Gonzales, R. J. (2015). The Implementation of an Innovative High School Mentoring Program Designed to Enhance Diversity and Provide a Pathway for Future Careers in Healthcare Related Fields.. Journal of racial and ethnic health disparities, 2(3), 395-402. doi:10.1007/s40615-015-0086-y
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  Although the population of diverse applicants applying to medical school has increased over recent years (AAMC Diversity in Medical Education: Facts and Figures 2012); efforts persist to ensure the continuance of this increasing trend. Mentoring students at an early age may be an effective method by which to accomplish diversity within the applicant pool. Having a diverse physician population is more likely able to adequately address the healthcare needs of our diverse population..The purpose of this study is to initiate a pipeline program, called the Medical Student Mentorship Program (MSMP), designed to specifically target high school students from lower economic status, ethnic, or racial underrepresented populations. High school students were paired with medical students, who served as primary mentors to facilitate exposure to processes involved in preparing and training for careers in medicine and other healthcare-related fields as well as research..Mentors were solicited from first and second year medical students at the University of Arizona College of Medicine-Phoenix (UACOM-P). Two separate cohorts of mentees were selected based on an application process from a local high school for the school years 2010-2011 and 2011-2012. Anonymous mentee and mentor surveys were used to evaluate the success of the MSMP..A total of 16 pairs of mentees and mentors in the 2010-2011 (Group 1) and 2011-2012 (Group 2) studies participated in MSMP. High school students reported that they were more likely to apply to medical school after participating in the program. Mentees also reported that they received a significant amount of support, helpful information, and guidance from their medical student mentors. Overall, feedback from mentees and mentors was positive and they reported that their participation was rewarding. Mentees were contacted 2 to 3 years post MSMP participation as sophomores or juniors in college, and all reported that they were on a pre-healthcare career track..The MSMP may serve as an effective pipeline program to promote future diversity in college and graduate training programs for future careers in science and medicine.
• Hale, T. M., Madhavpeddi, L., Hale, T. M., & Gonzales, R. J. (2014). Angiotensin II modulates sex steroid receptors and their metabolizing enzymes in rat cardiac fibroblast (701.10). The FASEB Journal, 28.
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  Sex steroids influence angiotensin II (AngII)-induced cardiac remodeling; however, the importance of local sex steroid metabolism in this process is not known. We previously demonstrated that AngII increased aromatase levels, the enzyme that converts testosterone (T) to 17β-estradiol, in cultured coronary vascular smooth muscle cells. In the present study we investigated the impact of AngII on sex steroid receptor and enzyme expression in primary rat cardiac fibroblasts. Fibroblasts were isolated from adult male rats and treated at P1 in 2% charcoal-stripped FBS with AngII or vehicle (18h), followed by T (6h) in the presence or absence of anastrozole (aromatase inhibitor; 6.5h). Cardiac fibroblasts expressed receptors ERα, ERβ, and AR, as well as the enzymes aromatase and 5α-reductase. AngII significantly reduced mRNA expression of ERβ. 5α-reductase, AR, and ERβ levels increased when anastrazole was administered with T. This is the first demonstration that cardiac fibroblasts express the enzymes and recep...
• Ramirez, A., O'connor, D. T., & Gonzales, R. J. (2014). 3β-Diol, an endogenous androgen, elicits relaxation via estrogen receptor activation in rat mesenteric and cerebral arteries (1156.15). The FASEB Journal, 28.
• Carroll, C. C., O'Connor, D. T., Steinmeyer, R., Del Mundo, J. D., McMullan, D. R., Whitt, J. A., Ramos, J. E., & Gonzales, R. J. (2013). The influence of acute resistance exercise on cyclooxygenase-1 and -2 activity and protein levels in human skeletal muscle. American journal of physiology. Regulatory, integrative and comparative physiology, 305(1).
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  This study evaluated the activity and content of cyclooxygenase (COX)-1 and -2 in response to acute resistance exercise (RE) in human skeletal muscle. Previous work suggests that COX-1, but not COX-2, is the primary COX isoform elevated with resistance exercise in human skeletal muscle. COX activity, however, has not been assessed after resistance exercise in humans. It was hypothesized that RE would increase COX-1 but not COX-2 activity. Muscle biopsies were taken from the vastus lateralis of nine young men (25 ± 1 yr) at baseline (preexercise), 4, and 24 h after a single bout of knee extensor RE (three sets of 10 repetitions at 70% of maximum). Tissue lysate was assayed for COX-1 and COX-2 activity. COX-1 and COX-2 protein levels were measured via Western blot analysis. COX-1 activity increased at 4 h (P < 0.05) compared with preexercise, but returned to baseline at 24 h (PRE: 60 ± 10, 4 h: 106 ± 22, 24 h: 72 ± 8 nmol PGH2·g total protein(-1)·min(-1)). COX-2 activity was elevated at 4 and 24 h after RE (P < 0.05, PRE: 51 ± 7, 4 h: 100 ± 19, 24 h: 98 ± 14 nmol PGH2·g total protein(-1)·min(-1)). The protein level of COX-1 was not altered (P > 0.05) with acute RE. In contrast, COX-2 protein levels were nearly 3-fold greater (P > 0.05) at 4 h and 5-fold greater (P = 0.06) at 24 h, compared with preexercise. In conclusion, COX-1 activity increases transiently with exercise independent of COX-1 protein levels. In contrast, both COX-2 activity and protein levels were elevated with exercise, and this elevation persisted to at least 24 h after RE.
• Gonzales, D. J., & Gonzales, D. J. (2013). Androgens and the cerebrovasculature: modulation of vascular function during normal and pathophysiological conditions. Pflügers Archiv : European journal of physiology, 465(5).
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  Sex steroids are commonly known for their contribution to phenotypic as well as biological reproductive sex differences mediated through classical regulation of neuroendocrine loops. However, sex steroids also have considerable impact on physiological function of non-reproductive tissues including the cerebrovasculature. Preclinical studies have shown that endogenous and exogenous administration of sex steroids significantly influences both cerebrovascular tone and brain function under normal conditions and following a pathological insult (e.g., middle cerebral artery occlusion). However, the precise mechanism(s) of how sex steroids modulate vasomotor responses and/or neurological outcomes in vivo is difficult to define since evidence based on both clinical and experimental studies has been shown to be dependent upon several variables including dose, duration of administration, presence of underlying pathologies, species, and sex. While progesterone, testosterone (TEST), and dihydrotestosterone (DHT) have all been investigated for their impact on the cerebral circulation, the effects of 17β-estradiol (E2) have been best characterized. Since recent reviews have highlighted studies reporting the actions of E2 on cerebral vascular function and health, only key points are included in this review. Conversely, less is known about the effect of androgens on the blood vessel wall, particularly in the cerebral circulation. The few studies that do address a role for androgen's modulation of cerebrovascular function under normal and pathophysiological conditions provide confounding evidence for either beneficial or detrimental effects. Therefore, the focus of this review is to highlight mechanisms associated with TEST, DHT, and its recently recognized androgen metabolite (3β-diol) on cerebrovascular function during healthy and diseased states.
• Gonzales, D. J., Zuloaga, K. L., O'Connor, D. T., Handa, R. J., & Gonzales, D. J. (2012). Estrogen receptor beta dependent attenuation of cytokine-induced cyclooxygenase-2 by androgens in human brain vascular smooth muscle cells and rat mesenteric arteries. Steroids, 77(8-9).
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  Androgens may provide protective effects in the vasculature under pathophysiological conditions. Our past studies have shown that dihydrotestosterone (DHT) decreases expression of cyclooxygenase-2 (COX-2) during cytokine, endotoxin, or hypoxic stimulation in human vascular smooth muscle cells, in an androgen receptor (AR)-independent fashion. Classically DHT is regarded as a pure AR agonist; however, it can be endogenously metabolized to 5α-androstane-3β, 17β-diol (3β-diol), which has recently been shown to be a selective estrogen receptor (ERβ) agonist. Therefore, we hypothesized that DHT's anti-inflammatory properties following cytokine stimulation are mediated through ERβ. Using primary human brain vascular smooth muscle cells (HBVSMC), we tested whether DHT's effect on IL-1β induced COX-2 expression was mediated via AR or ERβ. The metabolism of DHT to 3β-diol is a viable pathway in HBVSMC since mRNA for enzymes necessary for the synthesis and metabolism of 3β-diol [3alpha-hydroxysteroid dehydrogenase (HSD), 3β-HSD, 17β-HSD, CYP7B1] was detected. In addition, the expression of AR, ERα, and ERβ mRNA was detected. When applied to HBVSMC, DHT (10nM; 18 h) attenuated IL-1β-induced increases in COX-2 protein expression. The AR antagonist bicalutamide did not block DHT's ability to reduce COX-2. Both the non-selective estrogen receptor antagonist ICI 182,780 (1 μM) and the selective ERβ antagonist PHTPP (1 μM) inhibited the effect of DHT, suggesting that DHT actions are ERβ-mediated. In HBVSMC and in rat mesenteric arteries, 3β-diol, similar to DHT, reduced cytokine-induced COX-2 levels. In conclusion, DHT appears to be protective against the progression of vascular inflammation through metabolism to 3β-diol and activation of ERβ.
• Zuloaga, K. L., O'Connor, D. T., Handa, R. J., & Gonzales, R. J. (2012). Estrogen receptor beta dependent attenuation of cytokine-induced cyclooxygenase-2 by androgens in human brain vascular smooth muscle cells and rat mesenteric arteries.. Steroids, 8-9(77), 835-844.
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  PMID: 22542504
• Zuloaga, K. L., Swift, S. N., Gonzales, R. J., Wu, T. J., & Handa, R. J. (2012). The androgen metabolite, 5α-androstane-3β,17β-diol, decreases cytokine-induced cyclooxygenase-2, vascular cell adhesion molecule-1 expression, and P-glycoprotein expression in male human brain microvascular endothelial cells. Endocrinology, 153(12).
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  P-glycoprotein (Pgp), a multiple drug resistance transporter expressed by vascular endothelial cells, is a key component of the blood-brain barrier and has been shown to increase after inflammation. The nonaromatizable androgen, dihydrotestosterone (DHT), decreases inflammatory markers in vascular smooth muscle cells, independent of androgen receptor (AR) stimulation. The principal metabolite of DHT, 5α-androstane-3β,17β-diol (3β-diol), activates estrogen receptor (ER)β and similarly decreases inflammatory markers in vascular cells. Therefore, we tested the hypothesis that either DHT or 3β-diol decrease cytokine-induced proinflammatory mediators, vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2), to regulate Pgp expression in male primary human brain microvascular endothelial cells (HBMECs). Using RT-qPCR, the mRNAs for AR, ERα, and ERβ and steroid metabolizing enzymes necessary for DHT conversion to 3β-diol were detected in male HBMECs demonstrating that the enzymes and receptors for production of and responsiveness to 3β-diol are present. Western analysis showed that 3β-diol reduced COX-2 and Pgp expression; the effect on Pgp was inhibited by the ER antagonist, ICI-182,780. IL-1β-caused an increase in COX-2 and VCAM-1 that was reduced by either DHT or 3β-diol. 3β-diol also decreased cytokine-induced Pgp expression. ICI-182,780 blocked the effect of 3β-diol on COX-2 and VCAM-1, but not Pgp expression. Therefore, in cytokine-stimulated male HBMECs, the effect of 3β-diol on proinflammatory mediator expression is ER dependent, whereas its effect on Pgp expression is ER independent. These studies suggest a novel role of 3β-diol in regulating blood-brain barrier function and support the concept that 3β-diol can be protective against proinflammatory mediator stimulation.
• Zuloaga, K. L., Techapinyawat, R. A., & Gonzales, R. J. (2012). Dihydrotestosterone suppresses oxidative stress and improves vascular function following induction of inflammation in the cerebral circulation. The FASEB Journal, 26.
• Gonzales, D. J., Zuloaga, K. L., & Gonzales, D. J. (2011). Dihydrotestosterone attenuates hypoxia inducible factor-1α and cyclooxygenase-2 in cerebral arteries during hypoxia or hypoxia with glucose deprivation. American journal of physiology. Heart and circulatory physiology, 301(5).
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  Dihydrotestosterone (DHT) attenuates cytokine-induced cyclooxygenase-2 (COX-2) in coronary vascular smooth muscle. Since hypoxia inducible factor-1α (HIF-1α) activation can lead to COX-2 production, this study determined the influence of DHT on HIF-1α and COX-2 following hypoxia or hypoxia with glucose deprivation (HGD) in the cerebral vasculature. COX-2 and HIF-1α levels were assessed via Western blot, and HIF-1α activation was indirectly measured via a DNA binding assay. Experiments were performed using cerebral arteries isolated from castrated male rats treated in vivo with placebo or DHT (18 days) followed by hypoxic exposure ex vivo (1% O(2)), cerebral arteries isolated from castrated male rats treated ex vivo with vehicle or DHT (10 or 100 nM; 18 h) and then exposed to hypoxia ex vivo (1% O(2)), or primary human brain vascular smooth muscle cells treated with DHT (10 nM; 6 h) or vehicle then exposed to hypoxia or HGD. Under normoxic conditions, DHT increased COX-2 (cells 51%; arteries ex vivo 31%; arteries in vivo 161%) but had no effect on HIF-1α. Following hypoxia or HGD, HIF-1α and COX-2 levels were increased; this response was blunted by DHT (cells HGD: -47% COX-2, -34% HIF-1α; cells hypoxia: -29% COX-2, -54% HIF-1α; arteries ex vivo: -37% COX-2; arteries in vivo: -35% COX-2) and not reversed by androgen receptor blockade. Hypoxia-induced HIF-1α DNA-binding was also attenuated by DHT (arteries ex vivo and in vivo: -55%). These results demonstrate that upregulation of COX-2 and HIF-1α in response to hypoxia is suppressed by DHT via an androgen receptor-independent mechanism.
• Krause, D. N., Duckles, S. P., & Gonzales, R. J. (2011). Local estrogenic/androgenic balance in the cerebral vasculature.. Acta Physiologica, 181-186.
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  PMID: 21535417
• Techapinyawat, R. A., Osterlund, K. L., O'connor, D. T., & Gonzales, R. J. (2011). Inflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells. The FASEB Journal, 25.
• Zuloaga, K. L., & Gonzales, R. J. (2011). Dihydrotestosterone attenuates HIF-1alpha and Cyclooxygenase-2 in cerebral arteries following hypoxia or hypoxia with glucose deprivation. American Journal of Physiology Heart & Circulatory Physiology, 5(301), H1882-1890.
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  PMID: 21856910
• Gonzales, D. J., Osterlund, K. L., Handa, R. J., & Gonzales, D. J. (2010). Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells. American journal of physiology. Endocrinology and metabolism, 298(4).
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  Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues. Therefore, we tested the hypothesis that DHT alters COX-2 levels in the absence and presence of induced inflammation in primary human coronary artery smooth muscle cells (HCASMC). Furthermore, we tested the ancillary hypothesis that DHT's effects on COX-2 levels are AR-dependent. Cells were treated with DHT (10 nM) or vehicle for 6 h in the presence or absence of LPS or IL-1beta. Similar to previous observations in rodent arteries, in HCASMC, DHT alone increased COX-2 levels compared with vehicle. This effect of DHT was attenuated in the presence of the AR antagonist bicalutamide. Conversely, in the presence of LPS or IL-1beta, increases in COX-2 were attenuated by cotreatment with DHT. Bicalutamide did not affect this response, suggesting that DHT-induced decreases in COX-2 levels occur independent of AR stimulation. Thus we conclude that DHT differentially influences COX-2 levels under physiological and pathophysiological conditions in HCASMC. This effect of DHT on COX-2 involves AR-dependent and- independent mechanisms, depending on the physiological state of the cell.
• Osterlund, K. L., Handa, R. J., & Gonzales, R. J. (2010). Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells.. American Journal of Physiology Endocrinology and Metabolism., E838-E845.
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  PMID: 20103743
• Osterlund, K. L., Handa, R. J., & Gonzales, R. J. (2010). Dihydrotestosterone attenuates HIF-1alpha and COX-2 in cerebral arteries following hypoxia.. The FASEB Journal, 24.
• Gonzales, R. J., Duckles, S. P., & Krause, D. N. (2009). Dihydrotestosterone stimulates cerebrovascular inflammation through NFkappaB, modulating contractile function. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 29(2), 244-53.
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  Our previous studies show that long-term testosterone treatment augments vascular tone under physiological conditions and exacerbates endotoxin-induced inflammation in the cerebral circulation. However, testosterone can be metabolized by aromatase to estrogen, evoking a balance between androgenic and estrogenic effects. Therefore, we investigated the effect of the nonaromatizable androgen receptor agonist, dihydrotestosterone (DHT), on the inflammatory nuclear factor-kappaB (NFkappaB) pathway in cerebral blood vessels. Cerebral arteries were isolated from orchiectomized male rats treated chronically with DHT in vivo. Alternatively, pial arteries were isolated from orchiectomized males and were exposed ex vivo to DHT or vehicle in culture medium. DHT treatment, in vivo or ex vivo, increased nuclear NFkappaB activation in cerebral arteries and increased levels of the proinflammatory products of NFkappaB activation, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). Effects of DHT on COX-2 and iNOS were attenuated by flutamide. In isolated pressurized middle cerebral arteries from DHT-treated rats, constrictions to the selective COX-2 inhibitor NS398 or the selective iNOS inhibitor L-nil, [L-N6-(Iminoethyl)lysine], were increased, confirming a functional consequence of DHT exposure. In conclusion, activation of the NFkappaB-mediated COX-2/iNOS pathway by the selective androgen receptor agonist, DHT, results in a state of vascular inflammation. This effect may contribute to sex-related differences in cerebrovascular pathophysiology.
• Osterlund, K. L., Gutierrez, A., & Gonzales, R. J. (2009). Dihydrotestosterone (DHT) increases cyclooxygenase-2 (COX-2) in human coronary artery smooth muscle cells following IL-1{beta}-induced inflammation. The FASEB Journal, 23.
• Gonzales, R. J., Bryant, J. M., Naik, J. S., Resta, T. C., & Walker, B. R. (2008). Gender differences in mesenteric vasoconstrictor reactivity following chronic hypoxia. Microcirculation (New York, N.Y. : 1994), 15(6).
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  Male rats demonstrate persistent endothelium-dependent attenuation of vasoconstrictor reactivity following chronic hypoxia (CH). Since estrogen may interfere with hypoxia-induced gene expression, we hypothesized that gender differences exist in this response to CH. However, in conscious, instrumented rats, we found that CH resulted in a similar persistent reduction of pressor/total peripheral resistance responses to phenylephrine (PE) in rats of both genders. In contrast, although previous studies show mesenteric vascular responses to PE are reduced in CH males, we found that mesenteric reactivity was maintained in CH females. Since normoxic females demonstrate greater nitric oxide (NO) production, we hypothesized that the failure of CH to further diminish mesenteric reactivity in females was due to the inhibition of NO-dependent vasodilation. To test this hypothesis, constrictor reactivity of mesenteric arteries from male and female rats was examined. NO synthase (NOS) inhibition augmented constrictor responses to PE in arteries from both normoxic and CH males and normoxic females. In contrast, NOS inhibition had no effect in CH female vessels. Endothelial NOS (eNOS) levels were not different in arteries from control and CH females. Endothelial [Ca2+]i was greater in arterioles from CH females. Thus, CH reduces NO-dependent mesenteric dilation in females; this effect is not due to altered eNOS levels or diminished endothelial [Ca2+]i.
• Gonzales, R. J., Ansar, S., Duckles, S. P., & Krause, D. N. (2007). Androgenic/estrogenic balance in the male rat cerebral circulation: metabolic enzymes and sex steroid receptors. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 27(11).
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  Tissues from males can be regulated by a balance of androgenic and estrogenic effects because of local metabolism of testosterone and expression of relevant steroid hormone receptors. As a critical first step to understanding sex hormone influences in the cerebral circulation of males, we investigated the presence of enzymes that metabolize testosterone to active products and their respective receptors. We found that cerebral blood vessels from male rats express 5alpha-reductase type 2 and aromatase, enzymes responsible for conversion of testosterone into dihydrotestosterone (DHT) and 17beta-estradiol, respectively. Protein levels of these enzymes, however, were not modulated by long-term in vivo hormone treatment. We also showed the presence of receptors for both androgens (AR) and estrogens (ER) from male cerebral vessels. Western blot analysis showed bands corresponding to the full-length AR (110 kDa) and ERalpha (66 kDa). Long-term in vivo treatment of orchiectomized rats with testosterone or DHT, but not estrogen, increased AR levels in cerebral vessels. In contrast, ERalpha protein levels were increased after in vivo treatment with estrogen but not testosterone. Fluorescent immunostaining revealed ERalpha, AR, and 5alpha-reductase type 2 in both the endothelial and smooth muscle layers of cerebral arteries, whereas aromatase staining was solely localized to the endothelium. Thus, cerebral vessels from males are target tissues for both androgens and estrogen. Furthermore, local metabolism of testosterone might balance opposing androgenic and estrogenic influences on cerebrovascular as well as brain function in males.
• Krause, D. N., Gonzales, R. J., & Duckles, S. P. (2007). Dihydrotestosterone (DHT) differentially affects cerebral vascular inflammation in normoxia and hypoxia. The FASEB Journal, 21(6).
• Zhang, Y., Tamminga, S., Pelaez, N. J., & Gonzales, R. J. (2006). Student perceptions of their gains from a college-level human physiology lab. The FASEB Journal, 20(5).
• Gonzales, R. J., Ghaffari, A. A., Duckles, S. P., & Krause, D. N. (2005). Testosterone treatment increases thromboxane function in rat cerebral arteries. American journal of physiology. Heart and circulatory physiology, 289(2).
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  We previously showed that testosterone, administered in vivo, increases the tone of cerebral arteries. A possible underlying mechanism is increased vasoconstriction through the thromboxane A2 (TxA2) pathway. Therefore, we investigated the effect of chronic testosterone treatment (4 wk) on TxA2 synthase levels and the contribution of TxA2 to vascular tone in rat middle cerebral arteries (MCAs). Using immunofluorescence and confocal microscopy, we demonstrated that TxA2 synthase is present in MCA segments in both smooth muscle and endothelial layers. Using Western blot analysis, we found that TxA2 synthase protein levels are higher in cerebral vessel homogenates from testosterone-treated orchiectomized (ORX + T) rats compared with orchiectomized (ORX) control animals. Functional consequences of changes in cerebrovascular TxA2 synthase were determined using cannulated, pressurized MCA segments in vitro. Constrictor responses to the TxA2 mimetic U-46619 were not different between the ORX + T and ORX groups. However, dilator responses to either the selective TxA2 synthase inhibitor furegrelate or the TxA2-endoperoxide receptor (TP) antagonist SQ-29548 were greater in the ORX + T compared with ORX group. In endothelium-denuded arteries, the dilation to furegrelate was attenuated in both the ORX and ORX + T groups, and the difference between the groups was abolished. These data suggest that chronic testosterone treatment enhances TxA2-mediated tone in rat cerebral arteries by increasing endothelial TxA2 synthesis without altering the TP receptors mediating constriction. The effect of in vivo testosterone on cerebrovascular TxA2 synthase, observed here after chronic hormone administration, may contribute to the risk of vasospasm and thrombosis related to cerebrovascular disease.
• Sunday, L., Razmara, A., Krause, D. N., Gonzales, R. J., & Duckles, S. P. (2005). Gonadal hormones modulate LPS-induced inflammatory markers in rat cerebral blood vessels. Journal of Cerebral Blood Flow and Metabolism, 25(1_suppl), S111-S111. doi:10.1038/sj.jcbfm.9591524.0111
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  Following ischemic injury, activation of inflammatory mechanisms plays a significant role in cerebrovascular pathogenesis. In the rodent model, previous studies suggest that endogenous female sex steroids attenuate cerebral ischemia/reperfusion injury following experimental stroke. Because sex hormones modulate the outcome of ischemic injury in brain tissue, we investigated the impact of chronic in vivo estrogen or testosterone administration on cerebrovascular inflammation induced by the potent endotoxin, lipopolysaccharide (LPS). We hypothesized that estrogen will suppress, while testosterone will exacerbate the induction of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), important mediators of vascular inflammation contributing to the onset of cerebral tissue injury. The localization of LPS-induced COX-2 and iNOS protein was confirmed in both the endothelial and vascular smooth muscle layers of cerebral blood vessels using antibody specific staining and confocal microscopy. Initial experiments were performed to establish peak induction of COX-2 and iNOS protein levels in cerebral vessel homogenates from female and male rats using Western blot. Protein levels of COX-2 and iNOS were greatest at 6 hours post LPS (2 mg/kg i.p.) injection; thus this time point was selected to determine the effect of estrogen or testosterone on LPS-induced inflammation in cerebral blood vessels. Fischer-344 rats were gonadectomized and implanted with hormone filled pellets for 3 weeks. Orchiectomized male rats were treated without (ORX) or with either testosterone propionate (ORX+T) or 17 beta-estradiol (ORX+E). Ovariectomized female rats were treated without (OVX) or with 17 beta-estradiol (OVX+E). LPS treatment increased protein levels of both COX-2 and iNOS in cerebral blood vessels from all groups compared to saline (6 hr) injected controls. However, the induction of COX-2 and iNOS protein by LPS was significantly attenuated in cerebral vessels from OVX+E and ORX+E compared to OVX and ORX controls, respectively. In contrast, there was a marked increase in LPS-induced COX-2 and iNOS protein levels in cerebral vessels from ORX+T compared to ORX controls. In conclusion, it is likely that opposing actions of testosterone and estrogen to modulate cerebrovascular inflammation may contribute to the well-known gender differences clinically observed in stroke incidence and outcome.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2004). Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries. American journal of physiology. Heart and circulatory physiology, 286(2).
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  Little is known about vascular effects of testosterone. We previously reported chronic testosterone treatment increases vascular tone in middle cerebral arteries (MCA; 300 microm diameter) of male rats. In the present study, we investigated the hypothesis that physiological levels of circulating testosterone affect endothelial factors that modulate cerebrovascular reactivity. Small branches of MCA (150 microm diameter) were isolated from orchiectomized (ORX) and testosterone-treated (ORX+T) rats. Intraluminal diameters were recorded after step changes in intraluminal pressure (20-100 Torr) in the absence or presence of N(G)-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor; indomethacin, a cyclooxygenase (COX) inhibitor; and/or apamin and charybdotoxin (CTX); and K(Ca) channel blockers used to inhibit endothelium-derived hyperpolarizing factors (EDHF). At intraluminal pressures >or=60 Torr, arteries from ORX+T developed greater tone compared with ORX arteries. This difference was abolished by removal of the endothelium but remained after treatment of intact arteries with indomethacin or L-NAME. In addition, testosterone treatment had no effect on cerebrovascular production of endothelin-1 or prostacyclin nor did it alter protein levels of endothelial NOS or COX-1. Endothelium removal after L-NAME/indomethacin exposure caused an additional increase in tone. Interestingly, the latter effect was smaller in arteries from ORX+T, suggesting testosterone affects endothelial vasodilators that are independent of NOS and COX. Apamin/CTX, in the presence of L-NAME/indomethacin, abolished the difference in tone between ORX and ORX+T and resulted in vessel diameters similar to those of endothelium-denuded preparations. In conclusion, testosterone may modulate vascular tone in cerebral arteries by suppressing EDHF.
• Li, X., Geary, G. G., Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2004). Effect of estrogen on cerebrovascular prostaglandins is amplified in mice with dysfunctional NOS. American journal of physiology. Heart and circulatory physiology, 287(2), H588-94.
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  Chronic estrogen treatment increases endothelial vasodilator function in cerebral arteries. Endothelial nitric oxide (NO) synthase (eNOS) is a primary target of the hormone, but other endothelial factors may be modulated as well. In light of possible interactions between NO and prostaglandins, we tested the hypothesis that estrogen treatment increases prostanoid-mediated dilation using NOS-deficient female mouse models, i.e., mice treated with a NOS inhibitor [N(G)-nitro-l-arginine methyl ester (l-NAME)] for 21 days or transgenic mice with the eNOS gene disrupted (eNOS(-/-)). All mice were ovariectomized; some in each group were treated chronically with estrogen. Cerebral blood vessels then were isolated for biochemical and functional analyses. In vessels from control mice, estrogen increased protein levels of eNOS but had no significant effect on cyclooxygenase (COX)-1 protein, prostacyclin production, or constriction of pressurized, middle cerebral arteries to indomethacin, a COX inhibitor. In l-NAME-treated mice, however, cerebrovascular COX-1 levels, prostacyclin production, and constriction to indomethacin, as well as eNOS protein, were all greater in estrogen-treated animals. In vessels from eNOS(-/-) mice, estrogen treatment also increased levels of COX-1 protein and constriction to indomethacin, but no effect on prostacyclin production was detected. Thus cerebral blood vessels of control mice did not exhibit effects of estrogen on the prostacyclin pathway. However, when NO production was dysfunctional, the impact of estrogen on a COX-sensitive vasodilator was revealed. Estrogen has multiple endothelial targets; estrogen effects may be modified by interactions among these factors.
• Gonzales, R. J., & Walker, B. R. (2002). Role of CO in attenuated vasoconstrictor reactivity of mesenteric resistance arteries after chronic hypoxia. American journal of physiology. Heart and circulatory physiology, 282(1).
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  Chronic hypoxia (CH) is associated with a persistent reduction in systemic vasoconstrictor reactivity. Experiments on aortic ring segments isolated from CH rats suggest that enhanced vascular expression of heme oxygenase (HO) and resultant production of the vasodilator carbon monoxide (CO) may underlie this attenuated vasoreactivity after hypoxia. Similar to the aorta, small arteries from CH rats exhibit blunted reactivity; however, the regulatory role of CO in the resistance vasculature has not been established. Therefore, we examined the significance of HO activity on responsiveness to phenylephrine (PE) in the mesenteric circulation of control and CH rats. To document that the mesenteric bed demonstrates reduced reactivity after CH, we determined the vasoconstrictor responses of conscious, chronically instrumented male Sprague-Dawley rats to PE under control conditions and then immediately after exposure to 48 h CH (0.5 atm). All rats showed reduced mesenteric vasoconstriction to PE after CH. To examine the role of CO in reduced reactivity, small mesenteric arteries (100-200 microm intraluminal diameter) from control and 48-h CH rats were isolated and mounted on glass cannulas, pressurized to 60 mmHg and superfused with increasing concentrations of PE under normoxic conditions. Similar to the intact circulation, vessels from CH rats exhibited reduced vasoconstrictor sensitivity to PE compared with controls that persisted in the presence of nitric oxide synthase inhibition. The HO inhibitor, zinc protoporphyrin IX (5 microM) enhanced reactivity only in CH vessels. Additionally, a range of concentrations of the HO substrate heme-L-lysinate caused vasodilation in CH vessels but not in controls. Thus we conclude that CO contributes a significant vasodilator influence in resistance vessels after CH that may account for diminished vasoconstrictor responsiveness under these conditions.
• Walker, B. R., Kanagy, N. L., & Gonzales, R. J. (2001). 17beta-estradiol increases nitric oxide-dependent dilation in rat pulmonary arteries and thoracic aorta.. American journal of physiology. Lung cellular and molecular physiology, 280(3), L555-64. doi:10.1152/ajplung.2001.280.3.l555
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  Past studies have demonstrated that 17beta-estradiol (E(2)beta) increases endothelial nitric oxide (NO) synthase (eNOS) activity in uterine, heart, and skeletal muscle and in cultured human endothelial cells. However, little is known about E(2)beta regulation of NO synthesis in the pulmonary vasculature. The present study evaluated E(2)beta regulation of eNOS function in pulmonary arteries and thoracic aortas. We hypothesized that E(2)beta upregulates vascular NO release by increasing eNOS expression. To test this, NO-dependent vasodilation was assessed in isolated perfused lungs and aortic rings from ovariectomized Sprague-Dawley rats treated for 1 wk with 20 microg/24 h of E(2)beta or vehicle. Expression of eNOS was evaluated by Western blot and immunohistochemistry. Also, a RNase protection assay determined eNOS mRNA levels in lung and aortic homogenates from control and treated rats. Vasodilation to ionomycin in lungs from the E(2)beta-treated group was enhanced compared with that in control animals. Endothelium-intact aortic rings from E(2)beta-treated animals also demonstrated augmented endothelium-dependent dilation. Both responses were blocked with NOS inhibition. Immunostaining for eNOS was greater in pulmonary arteries and aortas from E(2)beta-treated compared with control rats. However, mRNA levels did not differ between groups. Thus we conclude that in vivo E(2)beta treatment augments endothelium-dependent dilation in aorta and lung, increasing expression of eNOS independently of sustained augmented gene transcription.
• Gonzales, R. J., Carter, R. W., & Kanagy, N. L. (2000). Laboratory demonstration of vascular smooth muscle function using rat aortic ring segments.. American Journal of Physiology: Advances in Physiology Education., 1(24), 13-21.
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  PMID: 11209559
• Kanagy, N. L., & Gonzales, R. J. (1999). Endothelium-Independent Relaxation of Vascular Smooth Muscle by 17beta-Estradiol.. Journal of cardiovascular pharmacology and therapeutics, 4(4), 227-234. doi:10.1177/107424849900400404
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  BACKGROUND: Estrogens directly dilate arteries, and this acute relaxation of vascular smooth muscle (VSM) may contribute to the cardioprotective effect of this important hormone. However, the mechanism by which estrogens relax VSM is not clear. METHODS AND RESULTS: Based on observations in isolated smooth muscle cells, we hypothesized that 17beta-estradiol (E(2)) causes dilation through receptor-mediated activation of K(+) channels in VSM cells. To test this hypothesis, E(2)-relaxation was studied in arteries from male Sprague-Dawley rats. We observed that the estrogen receptor antagonist, tamoxifen (3 µmol) attenuated E(2) relaxation, suggesting that at least a portion of the relaxation depends on activation of E(2) receptors. The nitric oxide synthase inhibitor, Nomega-nitro-larginine (100 µmol) did not affect E(2) relaxation in either denuded or endothelium-intact arterial strips. Furthermore, inhibition of guanylyl cyclase with LY83583 (10 µmol) had no effect on the relaxation, suggesting that nitric oxide does not contribute to this relaxation. Vascular segments contracted with 90 mmol KCl to disrupt the K(+) gradient had a similar E(2) relaxation does not require K(+)-channel activation. Finally, E(2) pretreatment inhibited contraction of arterial segments depleted of intracellular calcium but in the presence of extracellular calcium. However, E(2) did not affect contraction of strips in calcium-free solution. CONCLUSIONS: These final experiments suggest that E(2) inhibits Ca(2+) influx but not intracellular calcium release. Together, these studies establish that E(2) causes receptor-mediated relaxation of peripheral resistance arteries through inhibition of calcium entry independent of nitric oxide production, guanylyl cyclase stimulation, and K(+)-channel activation.
• Kanagy, N. L., & Gonzales, R. J. (1997). Mechanisms of direct relaxation of vascular smooth muscle by 17β-estradiol. The FASEB Journal, 11(3).
• Walker, B. R., Sanders, T. C., Resta, T. C., Gonzales, R. J., & Dail, W. G. (1997). Selective upregulation of arterial endothelial nitric oxide synthase in pulmonary hypertension.. The American journal of physiology, 272(2 Pt 2), H806-13. doi:10.1152/ajpheart.1997.272.2.h806
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  We have previously demonstrated that arterial, but not venous, vasodilatory responses to endothelium-derived nitric oxide (EDNO)-dependent agonists are enhanced in lungs isolated from rats with chronic hypoxia (CH)-induced pulmonary arterial hypertension. These data suggest that CH is associated with increased endothelial nitric oxide synthase (eNOS) activity within the pulmonary arterial vasculature. In addition, the correlation of increased pulmonary arterial pressure with selectively enhanced arterial responsiveness to EDNO-mediated agonists suggests that arterial hypertension, rather than hypoxia per se, is a contributing factor in this response. Therefore, we hypothesized that 1) CH selectively upregulates eNOS within the pulmonary arterial vasculature and 2) monocrotaline (MC)-induced pulmonary arterial hypertension selectively enhances pulmonary arterial dilation to EDNO-dependent dilators and upregulates arterial eNOS. We examined the responses to the EDNO-dependent dilators arginine vasopressin and ionomycin in U-46619-constricted isolated perfused lungs from control and MC-treated rats. Microvascular pressure was assessed by the double-occlusion technique, allowing calculation of segmental resistances. Lungs from MC-treated rats exhibited augmented arterial dilation to arginine vasopressin compared with control lungs. However, the responses to ionomycin were not different between the two groups. Quantitative immunocytochemistry was used to compare pulmonary eNOS immunoreactivity in vessels from control, CH, and MC-treated rats. eNOS staining was more intense in the arteries of CH and MC-treated rats compared with those of control animals, whereas CH and MC treatment had no effect on eNOS staining in veins. We conclude that pulmonary arterial hypertension, or altered vascular mechanical forces associated with hypertension, may be responsible for the augmented EDNO-dependent arterial dilation and upregulation of arterial eNOS in lungs from CH and MC-treated rats.
• Walker, B. R., Sanders, T. C., Resta, T. C., & Gonzales, R. J. (1996). Enhanced arterial dilation to arginine vasopressin in lungs from monocrotaline-treated rats. The FASEB Journal, 10(3).

Presentations

• Albrecht, A., Li, Y. ., Wendt, T., & Gonzales, R. J. (2019, October). S1PR1 Ligand Protects Against Hypoxia plus Glucose Deprivation-Induced Morphological Changes in Human Brain Vascular Smooth Muscle (2nd place oral Charles Tipton Undergraduate Symposium). Arizona Physiological Chapter Meeting. Tempe: Gonzales Lab.
• Ilhan, E., Chase, D., Roe, D., Thomas, N., Łaniewski, P., & Herbst-Kralovetz, M. (2019, spring). Vaginal microbiota, genital Inflammation, and HPV infection modulate cervicovaginal metabolomes in cervical carcinogenesis. Frontiers in Immunobiology & Immunopathogenesis Symposium, 2019, Tucson, AZ. Phoenix: UA.
• Li, Y., Shi, S., Liu, Q., Shi, F., & Gonzales, R. J. (2019, April). Selective Sphingosine-1-Phosphate Receptor-1 Ligand Protects Against Ischemia-Induced Inflammation and Dysfunction in Human Brain Microvascular Endothelial Cells (2nd place CardioVascular Pharm Division Postdoc/Graduate Student Symposium). Experimental Biology 2019. Orlando FL: Gonzales Lab.
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  2018 UA COMP Scholarly Project Symposium- February 6thInflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells. Rheana A Techapinyawat, Kristen L Zuloaga, Devin T O’Connor, and Rayna J Gonzales. Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, AZ 85004 USA
• Wendt, T., Li, Y., Albrecht, A., & Gonzales, R. J. (2019, October). S1PR-1 Activation Protects Against Ischemia-Induced Inflammation and Dysfunction in Human Brain Microvascular Endothelial Cells. Arizona Physiological Chapter Meeting. Tempe: Gonzales Lab.
• Raman, P., Madhavpeddi, L., & Gonzales, R. J. (2018, March). Palmitate Induces Glycosylation of Cyclooxygenase-2 in Primary Human Vascular Smooth Muscle Cells. ABRC VRP 2018 Symposium. Phoenix.
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  ABRC VRP 2018 Symposium- March 8thPalmitate Induces Glycosylation of Cyclooxygenase-2 in Primary Human Vascular Smooth Muscle Cells, Puneet Raman, Lakshmi Madhavpeddi, and Rayna J Gonzales, Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix. ***Selected for Oral Presentation
• Awwad, I., D'Lugos, A. C., Carroll, C. C., Gonzales, R. J., Sweazea, K. L., Dickinson, J. M., Angadi, S. S., & Hale, T. (2017, April). Exercise Preconditioning as A Means To Protect The Kidney Against Doxorubicin-Induced Oxidative Stress. Experimental Biology.
• Kerrigan, C., Raman, P., Rowe, R., Liftshitz, J., & Gonzales, R. (2015, October). Temporal expression of COX-2 following midline fluid percussion injury in the male rat brain. Arizona Chapter American Physiological Society Conference. Glendale, Arizona: APS.
• Bhatnagar, S., & Gonzales, R. J. (2014, June). Modulation of Palmitate on Vascular Health: Fat Chance?. BMS High School Summer Research Internship Symposium. ABC1 BMS COM-Phoenix.
• Madhavpeddi, L., Gonzales, R. J., & Hale, T. -. (2013, August). Local sex steroid hormone metabolism: Good for the heart!. BMS Intra-Departmental Seminar Series. University of Arizona COM-Phoenix: Department of Basic Medical Sciences.
• Madhavpeddi, L., Gonzales, R. J., & Hale, T. M. (2013, November). Angiotensin II Modulates Sex Steroid Receptors And Their Metabolizing Enzymes In Rat Cardiac Fibroblasts. American Physiological Society Arizona Chapter Meeting. Phoenix: American Physiological Society (Arizona Chapter).
• Patel, S., & Gonzales, R. J. (2013, February). Medical Student Mentoring Program: Analysis Update. BMS Intra-Departmental Seminar Series. University of Arizona COM-Phoenix: Department of Basic Medical Sciences.
• Prather, Z., & Gonzales, R. J. (2012, Spring). Androgen receptor expression in human coronary vascular smooth muscle cells during cytokine, angiotensin II, and hypoxia.. Scholarly Project Research Symposium. Phoenix, AZ.
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  (Selected as one of the top three presentations to be presented orally)
• Gonzales, R. J., O'Connor, D. T., Techapinyawat, R. A., & Osterlund, K. L. (2011, Spring). Inflammation-induced TLR4 expression and reactive oxygen species are attenuated by dihydrotestosterone in human primary vascular smooth muscle cells.. Experimental Biology. Washington, DC.
• Gonzales, R. J., Osterlund, K. L., O'Connor, D. T., & Techapinyawat, R. A. (2011, Spring). Androgens attenuate inflammation-induced TLR4 levels and oxidative stress in human primary brain vascular smooth muscle cells.. XXVth International Symposium of Cerebral Blood Flow, Metabolism, and Function. Barcelona, Spain.
• Osterlund, K. L., Handa, R. J., & Gonzales, R. J. (2011, Spring). Estrogen receptor beta-mediated anti-inflammatory effect of dihydrotestosterone during cytokine-induced inflammation in human brain vascular smooth muscle cells.. Experimental Biology. Washington DC.
• Osterlund, K. L., Handa, R. J., & Gonzales, R. J. (2011, Spring). Estrogen receptor beta-mediated anti-inflammatory effect of dihydrotestosterone during cytokine-induced inflammation in human brain vascular smooth muscle cells.. XXVth International Symposium of Cerebral Blood Flow, Metabolism, and Function. Barcelona, Spain.
• Osterlund, K. L., Handa, R. J., & Gonzales, R. J. (2010, Spring). Dihydrotestosterone attenuates HIF-1alpha and COX-2 in cerebral arteries following hypoxia.. Arizona Physiological Society Meeting. Glendale, AZ.
• Techapinyawat, R. A., Osterlund, K. L., & Gonzales, R. J. (2010, Spring). Androgen receptor agonist decreased reactive oxygen species in human coronary artery smooth muscle cells.. Arizona Physiological Society Meeting. Glendale, AZ.
• Gutierrez, A., Osterlund, K. L., & Gonzales, R. J. (2009, Spring). Dihydrotestosterone attenuates HIF-1alpha in cerebral arteries following hypoxia. Arizona Physiological Society Conference. Tucson AZ.
• Osterlund, K. L., & Gonzales, R. J. (2009, Spring). Dihydrotestosterone alters endotoxin and cytokine induced increases in cyclooxygenase-2 but has no effect on prostaglandin E2 levels in human coronary artery smooth muscle cells. Arizona Nevada Academy of Science. Tucson AZ: University of Arizona.
• Gonzales, R. J. (2008, Spring). DHT stimulates cerebrovascular inflammation through NFkB, modulating contractile function.. Arizona American Physiological Society. Tucson AZ: University of Arizona College of Medicine.
• Gonzales, R. J., Duckles, S. P., & Krause, D. N. (2008, Spring). Dihydrotestosterone enhances the NF kappa B pathway, modulating cerebral vascular function. Gordon Research Conference: Brain Energy Metabolism and Blood Flow. Andover, NH: Proctor Academy.
• Osterlund, K. L., & Gonzales, R. J. (2008, Spring). Dihydrotestosterone augments the proinflammatory mediator, COX-2, following IL1-beta stimulation in human brain microvascular endothelial cells.. Arizona American Physiological Society. Tucson AZ: University of Arizona College of Medicine.
• Gonzales, R. J. (2007, Spring). Dihydrotestosterone enhances the NFkB pathway modulating cerebral vascular function.. The American Physiological Society Sex and Gender Conference, Austin TX and Frontiers in Biomedical Research. Tucson, AZ.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2006, Spring). Dihydrotestosterone differentially modulates cyclooxygenase-2 following normoxia and hypoxia in rat cerebral arteries. American Heart Association Young Investigator Forum. San Francisco, CA.
• Bebenaz, E., Krause, D. N., Duckles, S. P., & Gonzales, R. J. (2005, Spring). The presence of gonadal hormone metabolic enzymes and androgen receptor in rat male cerebral blood vessels.. Southern California Conference for Undergraduate Research. UC Riverside, CA.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2005, Spring). Testosterone and estrogen modulate LPS-induced inflammation in rat cerebral blood vessels. American Heart Association Young Investigator Forum. Irvine, CA: University of California Irvine.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2005, Spring). The role of androgens on cerebral vascular function following inflammation: A potential implication for understanding stroke. Pre-Society for Neuroscience symposium. Irvine California: University of California Irvine.
• Ghaffari, A. A., Krause, D. N., Duckles, S. P., & Gonzales, R. J. (2004, Spring). Expression of aromatase in rat cerebral blood vessels: modulation by estrogen and medroxyprogesterone.. Experimental Biology. Washington D.C.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2004, Spring). Vascular effects of dihydrotestosterone in the cerebral circulation of male rats. American Heart Association Young Investigator Forum. Palo Alto, CA: Stanford University.
• Ghaffari, A. A., Krause, D. N., Duckles, S. P., & Gonzales, R. J. (2003, Spring). Effects of chronic medroxyprogesterone treatment on estrogen modulation of endothelial factors in rat cerebral arteries.. UC Leads and UROP. San Diego CA.
• Ghaffari, A. A., Krause, D. N., Duckles, S. P., & Gonzales, R. J. (2003, Spring). Modulation by testosterone of thromboxane production in middle cerebral arteries isolated from male rats.. American Association for Advancement in Science. Denver, CO.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2003, Spring). Endothelial modulation of pressure dependent tone by testosterone in rat cerebral arteries.. Experimental Biology. San Diego, CA.
• Marx, K. T., Krause, D. N., Duckles, S. P., & Gonzales, R. J. (2003, September). Activation of PI-3/Akt pathway by estrogen and testosterone in male cerebral blood vessels.. Southern California Conference for Undergraduate Research. UC Irvine, CA.
• Ghaffari, A. A., Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2002, Spring). Testosterone modulates non-nitric oxide, non-prostanoid endothelial-dependent vascular responses in rat cerebral arteries. Society for Advancement of Chicano and Native Americans in Science. Anaheim, CA.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2002, Spring). Testosterone modulates non-nitric oxide, non-prostanoid endothelial-dependent vascular responses in rat cerebral arteries. World Congress of Pharmacology and International Symposium on Vascular Neuroeffector Mechanisms. Lake Tahoe, CA.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2002, Spring). The effect of testosterone on thromboxane production and myogenic tone in middle cerebral arteries.. Myogenic Centennial 2002 Symposium. Stowe, VT.
• Ospina, J., Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2002, Spring). In vivo estrogen treatment alters vascular tone in resistance sized cerebral arteries of the rat via cyclooxygenase-dependent mechanisms.. World Congress of Pharmacology and International Symposium on Vascular Neuroeffector Mechanisms. San Francisco, CA.
• Gonzales, R. J., & Walker, B. R. (2001, Spring). Enhanced vasoconstrictor reactivity and vascular smooth muscle depolarization following chronic hypoxia in female rats.. APS conference: Genome and Hormones, an integrative approach to gender differences in physiology.

Poster Presentations

• Gallitano-Mendel, A. L., Hale, T., Herbst-Kralovetz, M., Gonzales, R. J., Titelbaum, A. R., Federico, G., Mahnert, N., Garcia-Filion, P., Omalley, C. W., Nelson, L. R., Muhammad, S., Parrish, J., Lucio, F., Mallin, E., Hartmark-Hill, J. R., Gulati, M., & Thomas, T. C. (2019, November). . Strategic initiative to create a Women in Medicine and Science (WIMS) program at a recently established and independently accredited College of Medicine. AAMC-Learn, Serve, Lead. Phoenix: AAMC.
• Gallitano-Mendel, A. L., Hale, T., Herbst-Kralovetz, M., Gonzales, R. J., Titelbaum, A. R., Federico, G., Mahnert, N., Garcia-Filion, P., Omalley, C. W., Nelson, L. R., Muhammad, S., Parrish, J., Lucio, F., Mallin, E., Hartmark-Hill, J. R., Gulati, M., & Thomas, T. C. (2019, November). Strategic initiative to create a Women in Medicine and Science (WIMS) program at a recently established and independently accredited College of Medicine. AAMC-Learn, Serve, Lead. Phoenix: AAMC.
• Li, Y., Shi, S., Liu, Q., Shi, F., & Gonzales, R. J. (2019, May). Selective sphingosine-1-phosphate receptor-1 as a potential therapeutic target for ischemic-induced injury in murine and human cerebrovasculature. Arizona Biomedical Research Center/Flinn Foundation Research Conference. Phoenix: Gonzales Lab.
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  2018 UA COMP Scholarly Project Symposium- February 6thInflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells. Rheana A Techapinyawat, Kristen L Zuloaga, Devin T O’Connor, and Rayna J Gonzales. Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, AZ 85004 USA
• Lyons, M., Albrecht, A., Li, Y. ., & Gonzales, R. J. (2019, July). Hypoxia plus Glucose Deprivation-Induced Morphological Changes in Human Brain Vascular Smooth Muscle Cells. BMS High School Internship Summer Reserach Symposium. Phoenix: Gonzales Lab.
• Raman, P., & Gonzales, R. J. (2019, April). Palmitate induces glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells (selected in top 5 for oral presentation). 2019 UA COMP Scholarly Project Symposium. Phoenix: UA COMP.
• Rodriquez, J., Shi, S., Eleanor, G., & Gonzales, R. J. (2019, April). Selective Estrogen Receptor Beta Agonist, 3beta-Diol, Attenuates Proinflammation Following Ischemic Injury in the Developing Brain. 2019 UA COMP Scholarly Project Symposium. Phoenix: UA COMP.
• Rodriquez, J., Shi, S., Gradidage, E., & Gonzales, R. J. (2019, April). 3beta-Diol Attenuates Cyclooxygenase-2 Following Ischemic Injury in the Developing Brain. 3rd Annual CareMore Cardiovascular Symposium. Tucson: Gonzales Lab.
• So, M., Trhin, T., Bartel, R., Sweazea, K., & Gonzales, R. J. (2019, March). Doxorubicin Temoporally Regulates Proinflammatory Meditor Production in Male and Female Human Vascular Smooth Muscle Cells.. 2019 UA COMP Scholarly Project Symposium. Phoenix: Gonzales Lab.
• So, M., Trhin, T., Bartel, R., Sweazea, K., & Gonzales, R. J. (2019, May). Doxorubicin Temporally Alters Human Vascular Smooth Muscle Cell Morphology and Density. Arizona Biomedical Research Center/Flinn Foundation Research Conference. Phoenix: Gonzales Lab.
• Thomas, T., Gulati, M., Jennifer, H., Gonzales, R. J., Mallin, E., Lucio, F., Parish, J., Muhammad, S., Nelson, L., O'Mally, C., Garcia-Filion, P., Manhnert, N., Frederico, G., Titelbaum, A., Hale, T., Herbst-Kralovetz, M., & Gallitano, A. (2019, November). Strategic initiative to create a Women in Medicine and Science (WIMS) program at a recently established and independently accredited College of Medicine. AAMC-Learn, Serve, Lead Conference. Phoenix: AAMC.
• Bartel, R., Rahman, S., Decort, B., Sweazea, K., & Gonzales, R. J. (2018, March). Lenalidomide Attenuates High Fat Diet Induced-Cyclooxygenase-2 Levels in Human Vascular Smooth Muscle Cells. 2018 Experimental Biology. San Diego: ASPET.
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  2018 Experimental Biology San DiegoLenalidomide Attenuates High Fat Diet Induced-Cyclooxygenase-2 Levels in Human Vascular Smooth Muscle Cells. Bartel R, Rahman S, DeCourt B, Sweazea KL, Gonzales RJ Dept. Basic Medical Sciences, UA COM Phoenix, School of Nutrition and Health Promotion, ASU, School of Life Sciences, ASU. ***Selected for ASPET Travel Award and Division for Cardiovascular Pharmacology in the Undergraduate Student category as a poster at the ASPET Student/Postdoc Poster Competition.
• D'Lugos, A., Fry, C., Hale, t., Gonzales, R. J., Angadi, S., & Dickenson, J. (2018, March). Impact of Chronic Doxorubicin Administration on the Satellite Cell Population and Capillary Density in Multiple Skeletal Muscles. 2018 Experimental Biology. San Diego: ASPET.
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  2018 Experimental Biology San DiegoThe Impact of Chronic Doxorubicin Administration on the Satellite Cell Population and Capillary Density in Multiple Skeletal Muscles. Andrew C D’Lugos, Christopher S Fry, Taben M Hale, Rayna J Gonzales, Siddhartha S Angadi, Chad C Carroll, Jared M Dickinson. Dept. Basic Medical Sciences, UA COM Phoenix, School of Nutrition and Health Promotion, ASU
• Li, Y., Rahman, S., Shi, F., & Gonzales, R. J. (2018, March). Selective S1PR1 Modulator Attenuates Hypoxia plus Glucose Deprivation-Induced COX-2 in Human Brain Vascular Smooth Muscle Cells. 2018 Arizona Physiological Society's 10th Annual Meeting. Tempe: American Physiological Society.
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  2018 Arizona Physiological Society's 10th Annual MeetingSelective S1PR1 Modulator Attenuates Hypoxia plus Glucose Deprivation-Induced COX-2 in Human Brain Vascular Smooth Muscle Cells. Li YJ, Rahman S, Shi, FD, Gonzales RJ. School of Life Sciences, Arizona State University, Tempe, AZ, Barrow Neurological Institutes, Phoenix, AZ, University of Arizona College of Medicine - Phoenix, Phoenix, AZ. ***Selected out of 56 abstracts to be presented as the top 3 postdoctoral oral presentations.
• Mohamed, A., Shi, S., Jin, W., Liu, Q., Shi, F., & Gonzales, R. J. (2018, March). Region Specific Sphingosine-1-Phosphate Receptor 1 Expression in Male and Female Murine Brain following Acute Ischemia and Reperfusion. 2018 UA COMP Scholarly Project Symposium. Phoenix.
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  2018 UA COMP Scholarly Project Symposium- February 6thRegion Specific Sphingosine-1-Phosphate Receptor 1 Expression in Male and Female Murine Brain following Acute Ischemia and Reperfusion. Mohamed A, Shi S1, Shi K, Jin W, Liu Q, Shi F, and Gonzales RJ, Department of Basic Medical Sciences at University of Arizona College of Medicine Phoenix and Department of Neurobiology at Barrow Neurological Institute
• Rahman, S., Li, Y., Sweazea, K., & Gonzales, R. J. (2018, March). Hypoxia plus Deprivation Increases NF-κB Activation and Downstream Pro-Inflammatory Enzyme Levels in Human Brain VSM Cells. 2018 Arizona Physiological Society's 10th Annual Meeting. Tempe: American Physiological Society.
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  2018 Arizona Physiological Society's 10th Annual MeetingHypoxia plus Deprivation Increases NF-κB Activation and Downstream Pro-Inflammatory Enzyme Levels in Human Brain VSM Cells. Rahman S, Li YJ, Sweazea K, Gonzales RJ, School of Nutrition and Health Promotion and School of Life Sciences, Arizona State University, Tempe, AZ and University of Arizona College of Medicine - Phoenix, Phoenix, AZ ***Selected for oral presentation. Awarded 1st place Undergraduate Oral Presentation
• Shi, S., Mohamed, A., Shi, K., Jin, W., Gonzales, R. J., Liu, Q., & Shi, F. (2018, March). RP101075, Novel SPR1 Ligand Protects Against Acute Cerebral Ischemia. ABRC VRP 2018 Symposium. Phoenix.
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  ABRC VRP 2018 Symposium- March 8thRP101075, Novel SPR1 Ligand Protects Against Acute Cerebral Ischemia. Samuel Shi, Awad Mohamed, Shi Kiabin, Weina Jin, Qiang Liu, Fu-Dong Shi and Rayna J Gonzales, Dept. of Basic Medical Sciences at University of Arizona College of Medicine Phoenix and Dept. of Neurobiology at Barrow Neurological Institute
• Shi, S., Mohamed, A., Shi, K., Jin, W., Shi, F., Liu, Q., & Gonzales, R. J. (2018, March). Differential Sphingosine-1-Phosphate Receptor 1 Expression in Male and Female Murine Heart and Brain following Middle Cerebral Artery Occlusion and Reperfusion. 2018 Experimental Biology. San Diego: ASPET.
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  2018 Experimental Biology San DiegoDifferential Sphingosine-1-Phosphate Receptor 1 Expression in Male and Female Murine Heart and Brain following Middle Cerebral Artery Occlusion and Reperfusion. Shi S, Mohamed A, Shi K, Jin W, Shi F, Liu Q, and Gonzales RJ. Dept. of Basic Medical Sciences at University of Arizona College of Medicine PhoenixDept. of Neurobiology at Barrow Neurological Institute. ***Selected for ASPET Datablitz- top 10 highlighted rapid fire talks.
• So, M., Bartel, R., Tat, T., Sweazea, K., & Gonzales, R. J. (2018, March). Doxorubicin Temporally Modulates Cyclooxygenase-2 Levels in Male and Female Human Vascular Smooth Muscle Cells. ABRC VRP 2018 Symposium. Phoenix.
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  ABRC VRP 2018 Symposium- March 8thDoxorubicin Temporally Modulates Cyclooxygenase-2 Levels in Male and Female Human Vascular Smooth Muscle Cells. Mei So, Robyn Bartel, Trinh Tat, Karen Sweazea, and Rayna J Gonzales. Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ School of Nutrition and Health Promotion, Arizona State University, Tempe AZ
• Tat, T., Bartel, R., So, M., Sweazea, K., & Gonzales, R. J. (2018, March). Doxorubicin Temporally Modulates Cyclooxygenase-2 Levels in Male and Female Human Vascular Smooth Muscle Cells. 2018 Experimental Biology. San Diego: ASPET.
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  2018 Experimental Biology San DiegoDoxorubicin Temporally Modulates Cyclooxygenase-2 Levels in Male and Female Human Vascular Smooth Muscle Cells. Tat T, Bartel R, So M, Sweazea K, and RJ Gonzales, Dept. Basic Medical Sciences, UA COM Phoenix, School of Nutrition and Health Promotion, ASU. ***Selected for ASPET Travel Award and Division for Cardiovascular Pharmacology in the Undergraduate Student category as a poster at the ASPET Student/Postdoc Poster Competition.
• Tat, T., So, M., Bartel, R., Sweazea, K., & Gonzales, R. J. (2018, March). Doxorubicin Temporarily Modulates Cyclooxygenase-2 Levels in Male and Female Human Vascular Smooth Muscle Cells. UA UBRP Conference. Tucson: Undergraduate Biology Research Program.
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  2018 UBRP ConferenceDoxorubicin Temporarily Modulates Cyclooxygenase-2 Levels in Male and Female Human Vascular Smooth Muscle Cells. T Tat, M So, R Bartel, K Sweazea and RJ Gonzales, Department of Basic Medical Sciences University of Arizona College of Medicine-Phoenix, School of Nutrition and Health Promotion, Arizona State University,
• Techapinyawat, R., Zuloaga, K., O'Conner, D., & Gonzales, R. J. (2018, March). Inflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells. 2018 UA COMP Scholarly Project Symposium. Phoenix.
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  2018 UA COMP Scholarly Project Symposium- February 6thInflammation-Induced TLR4 Expression and Reactive Oxygen Species are Attenuated by Dihydrotestosterone in Human Primary Vascular Smooth Muscle Cells. Rheana A Techapinyawat, Kristen L Zuloaga, Devin T O’Connor, and Rayna J Gonzales. Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, AZ 85004 USA
• Awwad, I., D'Lugos, A. C., Carroll, C. C., Gonzales, R. J., Sweazea, K. L., Dickinson, J. M., Angadi, S. S., & Hale, T. (2017, April). Exercise Preconditioning as A Means To Protect The Kidney Against Doxorubicin-Induced Oxidative Stress. Experimental Biology.
• Gonzales, R. J., & Raman, P. (2014, April). Palmitate-Induced Glycosylation of Cyclooxygenase-2 in Primary Human Brain and Aortic Vascular Smooth Muscle Cells. Experimental Biology. Boston.
• Gonzales, R. J., & Raman, P. (2017, April). Glucosamine Hydrochloride and Tunicamycin Attenuate Palmitate-Induced Glycosylation of Cyclooxygenase-2 in Primary Human Vascular Smooth Muscle Cells. Experimental Biology 2017. Chicago IL: American Physiological Society and the American Society of Pharmacology and Experimental Theraputics.
• Gonzales, R. J., & Raman, P. (2017, March). Palmitate-Induced Glycosylation of Cyclooxygenase-2 in Human Vascular Smooth Muscle Cells. ABRC VRP 2017 Symposium. COM-Phx Phoenix AZ.
• Gonzales, R. J., Angadi, S., & Dickenson, J. (2017, March). High-intensity interval exercise preconditioning protects against doxorubicin-mediated cardiotoxicity. Exercise Metabolism Conference. Goteberg , Sweden.
• Gonzales, R. J., Angadi, S., Jarret, C., Pankinin, T., D'Lugos, A., Hale, T., Carrol, C., & Dickenson, J. (2017, June). High-Intensity Interval Exercise Preconditioning Protects Against Doxorubicin Medicated Cardiotoxicity.. 2017 ASU Cell Symposium. ASU Tempe AZ.
• Gonzales, R. J., Bartel, R., Rahman, S., Decourt, B., & Sweazea, K. (2017, October). Lenalidomide attenuates high fat diet induced cyclooxygenase-2 levels in primary human vascular smooth muscle cells. 2017 Arizona Physiological Society's 10th Annual Meeting. NAU Flagstaff AZ.
• Gonzales, R. J., Bartel, R., Sweazea, K., & So, M. (2017, March). Doxorubicin temporally modules cyclooxygenase-2 levels in human vascular smooth muscle cells. 2017 Arizona Physiological Society's 10th Annual Meeting. NAU Flagstaff AZ.
• Gonzales, R. J., Raman, P., & Tat, T. (2017, April). Doxorubicin Dose Dependently Attenuates Cyclooxygenase-2 in Female Human Coronary Vascular Smooth Muscle Cells. Experimental Biology 2017. Chicago IL: American Physiological Society and the American Society of Pharmacology and Experimental Theraputics.
• Gonzales, R. J., Shi, S., & Liu, Q. (2017, April). Dihydrotestosterone Mediates Neuroprotective Effects via Estrogen Receptor Beta Following Brain Ischemia-Reperfusion Injury in Male Mice. Experimental Biology 2017. Chicago IL: American Physiological Society and the American Society of Pharmacology and Experimental Theraputics.
• Gonzales, R. J., Shi, S., Gradidge, E., & Liu, Q. (2017, April). Androgens Mediate Neuroprotection via Estrogen Receptor Beta Following Brain Ischemia-Reperfusion Injury in Male Mice. 2017 UACOM-Phoenix Research Symposium. UA COM-Phx Phoenix AZ.
• Gonzales, R. J., Shi, S., Mohamad, A., Rodriquez, J., & Liu, Q. (2017, March). Differential sphingosine-1-phosphate receptor 1 expression following middle cerebral artery occlusion in murine heart and brain. 2017 Arizona Physiological Society's 10th Annual Meeting. NAU Flaggstaff AZ.
• Gonzales, R. J., Tat, T., Raman, P., & Vijayaval, N. (2017, March). Doxorubicin Attenuates Proinflammatory Mediators in Female Human Coronary Vascular Smooth Muscle Cells.. University of Arizona Biological, Engineering, Chemical Undergraduate Research Symposium. Tucson.
• Gonzales, R. J., Tat, T., So, M., & Lopez, J. (2017, July). Doxorubicin Alters Cyclooxygenase-2 Levels in Human Brain Vascular Smooth Muscle Cells.. BMS High School Research Internship Symposium. Phoenix AZ.
• Gonzales, R. J., Tat, T., Vijayavel, N., Raman, P., Angadi, S., & Dickenson, J. (2017, March). Doxorubicin Dose Dependently Attenuates Cyclooxygenase-2 Levels in Human Coronary Vascular Smooth Muscle Cells. UA UBRP Conference. Tucson: Undergraduate Biology Research Program.
• Awwad, I. M., D'Lugos, A. C., Carroll, C. C., Gonzales, R. J., Sweazea, K. L., Dickinson, J. M., Angadi, S. S., & Hale, T. (2016, October). Exercise Preconditioning as a Means to Protect Against Doxorubicin-Induced Renal Injury. Arizona Physiological Soceity.
• Bilal, K., Perez, O., D'Lugos, A. C., Carroll, C. C., Gonzales, R. J., Sweazea, K. L., Dickinson, J. M., Angadi, S. S., & Hale, T. (2016, October). Impact of High Intensity Interval Training on Doxorubicin-Induced Pathological Cardiac Remodeling in Female Sprague Dawley Rats. Arizona Physiological Soceity.
• D'Lugos, A., Cosgrave, C., Cosgrave, C., Dedmon, C., Astill, B., Patel, S., Katsma, M., Gonzales, R. J., Hale, T., Carroll, C., Dickinson, J., & Angadi, S. (2016, April). High Intensity Exercise Preserves Myocellular Size Throughout Doxorubicin Treatment.. American Physiological Society Intersociety Meeting, Integrative Biology of Exercise VII. Phoenix AZ: APS.
• D'Lugos, A., Mahmood, T., Salvo, L., Ormsby, j., Cosgrove, C., Hale, t., Dedmon, D., Gonzales, R., Carroll, C., Angadi, S., & Dickinson, J. (2016, April). High Intensity Exercise Preserves Myocellular Size and mTOR Signaling During Doxorubicin Treatment. Alternative Muscle Club Meeting. San Diego CA: Alternative Muscle Club Meeting.
• Dickinson, J., D'Lugos, A., Mahmood, T., Gonzales, R. J., Cosgrave, C., Hale, T., Cosgrave, C., Dedmon, C., Astill, B., Patel, S., Angadi, S., & Carroll, C. (2016, April). High Intensity Exercise Preserves Skeletal Muscle Motor Signaling During Doxorubicin Treatment in Ovariectomized Female Rats. American Physiological Society Intersociety Meeting, Integrative Biology of Exercise VII. Phoenix AZ: APS.
• Jarrett, C., D'Lugos, A., Mahmood, A., Gonzales, R. J., Hale, T., Carroll, C., Patel, S., Cosgrave, C., Dedmon, C., Astill, B., Dickinson, J., & Angadi, S. (2016, April). Associations Between Antioxident Enzymes in Cardiomyocytes and Skeletal Muscle During Doxorubicin Treatment. American Physiological Society Intersociety Meeting, Integrative Biology of Exercise VII. Phoenix AZ: APS.
• Perez, O., Abidali, H., D'Lugos, A. C., Carroll, C. C., Gonzales, R. J., Sweazea, K. L., Dickinson, J. M., Angadi, S. S., & Hale, T. (2016, October). Impact of High Intensity Interval Training on Doxorubicin-Induced Cardiotoxicity in Female Sprague Dawley Rats. Arizona Physiological Soceity.
• Raman, P., Tat, T., & Gonzales, R. J. (2016, October). Glucosamine hydrochloride and tunicamycin attenuate palmitate-induced glycosylation of cyclooxygenase-2 in primary human vascular smooth muscle cells. Experimental Biology 2017. Chicago IL: ASPET.
• So, M., Tat, T., Vijayavel, N., Raman, P., Dickinson, J., Angadi, S., & Gonzales, R. J. (2016, April). Doxorubicin dose dependently attenuates cyclooxygenase-2 expression in female human coronary vascular smooth muscle. Arizona Chapter American Physiological Society Conference. Tucson: APS.
• Tat, T., So, M., Vijayavel, N., Raman, P., Dickinson, J., Angadi, S., & Gonzales, R. (2016, April). Anthracycline toxicity alters TLR4/NFkappaB/COX-2 in female human coronary vascular smooth muscle cells **ASPET SURF Fellow. Undergraduate Biology Research Program (UBRP) Symposium. Tucson: ASPET.
• Vijayavel, N., Raman, P., Sweazea, K., Sweazea, K., Dickinson, J., Angadi, S., & Gonzales, R. J. (2016, April). Doxorubicin attenuates proinflammatory mediator expression in brain and pial arteries from ovariectomized female rats independent of high intensity exercise. Arizona Chapter American Physiological Society Conference. Phoenix AZ: APS.
• Vijayavel, N., So, M., Tat, T., Raman, P., Hale, T., Sweazea, K., Dickinson, J., Angadi, S., & Gonzales, R. J. (2016, April). Doxorubicin reduces proinflammatory mediator expression in brain and pial arteries from ovariectomized female rats independent of high intensity exercise. American Physiological Society Intersociety Meeting, Integrative Biology of Exercise VII. Phoenix AZ: APS.
• D'Lugos, A., Mahmood, T., Cograve, C., Dedmon, W., Astill, B., Patel, S., Katsma, M., Gonzales, R., Hale, T., Carroll, C., Angati, S., & Dickinson, J. (2015, October). High intensity exercise preserves doxorubicin skeletal muscle atrophy in ovariectomized female rats. Arizona Chapter American Physiological Society Conference. Glendale, Arizona: APS.
• Gonzales, R. J. (2015, September). Cerebrovascular Physiology and Sex Steroid Biology. Valley Research Partnership Collaboration Fair. UA COM-Phoenix: Valley Research Partnership.
• Gonzales, R., Raman, P., Vijayavel, N., Kerrigan, C., Echeverria, J., Hale, T., Carol, C., Dickinson, J., & Angadi, S. (2015, November). Doxorubicin reduces proinflammatory mediator expression in brain and pial arteries from ovariectomized female rats. American Physiological Society: Cardiovascular, Renal and Metabolic Diseases: Physiology and Gender. Annapolis, Maryland: APS.
• Kerrigan, C., Raman, P., Rowe, R., Liftshitz, J., & Gonzales, R. (2015, October). Temporal expression of COX-2 following midline fluid percussion injury in the male rat brain. Arizona Chapter American Physiological Society Conference. Glendale, Arizona: APS.
• Madhavpeddi, L., Hale, T., & Gonzales, R. J. (2015, November). Angiotensin II modulates sex steroid metabolizing enzyme and receptor expression in cardiac fibroblast from male and female rats. American Physiological Society: Cardiovascular, Renal and Metabolic Diseases: Physiology and Gender. Annapolis, Maryland: The American Physiological Society.
• Mahmood, T., D'Lugos, A., Dedmon, W., Astill, B., Patel, S., Katsma, M., Gonzales, R., Hale, T., Carroll, C., Angati, S., & Dickinson, J. (2015, October). High intensity exercise protects skeletal muscle from complications of doxorubicin treatment. Arizona Chapter American Physiological Society Conference. Glendale, Arizona: APS.
• Raman, P., Gonzales, R., & Techapinyawat, R. (2015, June). Saturated fatty acid-induced glycosylation in primary human vascular smooth muscle cells. BMS 2015 Symposium. Phoenix, Arizona: Department of Basic Medical Sciences.
• Raman, P., Techpinyawat, R., & Gonzales, R. (2015, April). Palmitate-induced glycosylation in human vascular smooth muscle cells. Experimental Biology. Boston, Massachusettes: APS and ASPET.
• Shi, S., Liu, Q., & Gonzales, R. (2016, April). Dihydrotestosterone mediates neuroprotection following ischemic injury in male mice. 7th Annual ASU BNI Neuroscience Symposium. Tempe AZ.
• Shi, S., Liu, Q., & Gonzales, R. J. (2016, October). Dihydrotestosterone via ERbeta reduces lesion size following ischemic injury in male mice (**Invited oral presentation). Arizona Chapter American Physiological Society Conference. Tucson AZ: APS.
• Vijayavel, N., Raman, P., Kerrigan, C., Echeverria, J., Dickinson, J., Carol, C., Angadi, S., & Gonzales, R. (2015, October). Doxorubicin reduces proinflammatory mediator expression in brain and pial arteries from ovariectomized female rats. Arizona Chapter American Physiological Society Conference. Glendale, Arizona: APS.
• Gonzales, R. J. (2014, October). Unraveling the Vascular Mysteries of Stroke: Strategies. University of Arizona Foundation and Presidents Club beyond the Boundaries EXPO. Arizona Biltmore, Phoenix AZ.
• Gonzales, R. J., Ramirez, A., & O'Connor, D. (2014, April). 3-beta Diol Elicits Relaxation via Estrogen Receptor Activation in Rat Mesenteric and Cerebral Arteries. Experimental Biology. San Diego: APS/ASPET.
• Madhavpeddi, L., Gonzales, R. J., & Hale, T. M. (2014, April). Angiotensin II Modulates Sex Steroid Receptors and their Metabolizing Enzymes in Rat Cardiac Fibroblast. Experimental Biology.
• Madhavpeddi, L., Hale, T. M., & Gonzales, R. J. (2014, November). Impact of Angiotensin II on Sex Steroid Receptors in Human Aortic Smooth Muscle Cells. Arizona Chapter American Physiological Society.
• Madhavpeddi, L., Hale, T., & Gonzales, R. J. (2014, Octovber). Impact of angiotensin II on sex steroid receptors in human aortic smooth muscle cells. Arizona Chapter American Physiological Society. Tucson.
• Raman, P., & Gonzales, R. J. (2014, October). Palmitate Increases Glycosylation of Cyclooxygenase-2 in Primary Human Vascular Smooth Muscle Cells. Arizona Chapter American Physiological Society. Tucson.
• Gonzales, R. J., Madhavpeddi, L., & O'Connor, D. (2013, June). Endothelial dependent dilation mediated by estrogen receptor bets activation in the rat mesenteric and cerebrovasculature. BMS Research Retreat. Cave Creek Arizona: Department of Basic Medical Sciences.
• Gonzales, R. J., Ramen, P., O'Connor, D., & Madhavpeddi, L. (2013, October). Lipopolysaccharide and interleukin-1 beta modulate estrogen receptor beta in rat mesenteric and pial arteries as well as human coronary artery vascular smooth muscle cells. American Physiological Arizona Chapter Meeting. Phoenix: American Physiological Society.
• Gonzales, R. J., Ramirez, A., & O'Connor, D. (2013, October). Vasoactive effects of a novel endogenous androgen are mediated by estrogen receptor activation in the rat mesenteric and cerebrovasculature. American Physiological Arizona Chapter Meeting. Phoenix: American Physiological Society.
• Madhavpeddi, L., Gonzales, R. J., & Hale, T. -. (2013, June). Angiotensin II modulates sex steroid receptors and their metabolizing enzymes in rat cardiac fibroblasts. BMS Retreat. Cave Creek Arizona: Department of Basic Medical Sciences.
• Madhavpeddi, L., Gonzales, R. J., & Hale, T. -. (2013, October). Angiotensin II modulates sex steroid receptors and their metabolizing enzymes in rat cardiac fibroblasts. American Physiological Arizona Chapter Meeting. Phoenix, AZ. Phoenix: American Physiological Society.
• Madhavpeddi, L., Gonzales, R. J., & Hale, T. M. (2013, November). Angiotensin II Modulates Sex Steroid Receptors And Their Metabolizing Enzymes In Rat Cardiac Fibroblasts. Arizona Physiological Society. Phoenix: AZPS.
• O'Connor, D. T., Osterlund, K. L., Steinmeyer, R. N., & Gonzales, R. J. (2010, Spring). Endotoxin- or hypoxic-induced TLR4 expression is blunted by dihydrotestosterone in primary human vascular smooth muscle cells.. Arizona Physiological Society Meeting. Glendale, AZ.
• Osterlund, K. L., Techapinyawat, R. A., O'Connor, D. T., Steinmeyer, R. N., & Gonzales, R. J. (2010, Spring). Inflammation-induced TLR4 expression and reactive oxygen species are attenuated by dihydrotestosterone in human primary vascular smooth muscle cells.. Arizona Health Science Center Frontiers in Biomedical Science Poster Session. Tucson, AZ.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2004, Spring). Effect of testosterone on the thromboxane pathway in rat middle cerebral arteries.. UCI SOM Faculty Research Poster Session. Irvine, CA.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2003, Spring). Testosterone modulates non-nitric oxide, non-prostanoid endothelial dependent vascular responses in rat cerebral arteries.. Faculty Research Poster Session, 10th Annual College of Medicine Celebration of Research. Irvine, CA: University of Irvine.

Creative Productions

• Gonzales, R. J. (2015. Bristol-Myers Squibb Scientist and his team of colleagues recently awarded The American Chemical Society 2015 Heroes of Chemistry Award. Members in the News: Achievements, Awards, Promotions, and Scientific BreakthroughsAmerican Society for Experimental Therapuetics and Pharmacology. http://issuu.com/aspetpublications/docs/14451_sept_2015_aspet_tpharm_web?e=17904823/15321583
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  Write submission entries as communication officer for the cardiovascular pharmacology division of ASPET in "Members Achieve" Section of the Pharmacologist published quarterly. Example of published piece at URL.
• Gonzales, R. J. (2015. University of Houston Scientist Awarded NIH Funding to Study Scaffolding Protein Interaction Network Regulates Cardiac Cell Signaling. Members in the News: Achievements, Awards, Promotions, and Scientific BreakthroughsAmerican Society for Experimental Therapuetics and Pharmacology. http://issuu.com/aspetpublications/docs/14451_sept_2015_aspet_tpharm_web?e=17904823/15321583
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  Write submission entries as communication officer for the cardiovascular pharmacology division of ASPET in "Members Achieve" Section of the Pharmacologist published quarterly. Example of published piece at URL.

Others

• Gonzales, R. J. (2012, July). Representative spokesperson. Sarver Heart Center and Fall Classic Alliance Beverage Fundraising Golf Tournament.
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  Promotional videotape interview speaking about the impact community support has on biomedical research in Arizona
• Gonzales, R. J. (2012, September). Reporter Interview. Equal Opportunity Magazine for Career Guidance and Recruitment.
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  Interview highlighting the career opportunities for biomedical professionalsPhoenix, AZ
• Gonzales, R. J., Techapinyawat, R. A., O'Connor, D. T., & Zuloaga, K. L. (2012, Spring). Dihydrotestosterone suppressed oxidative stress and augments vascular function following induction of inflammation in the cerebral circulation.. Experimental Biology.
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  San Diego, CA
• O'Connor, D. T., Hale, T. -., Rodriguez, P. A., & Gonzales, R. J. (2012, Spring). The life of a physiologist at the University of Arizona COM-Phoenix.. Experimental Biology.
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  San Diego, CA
• Osterlund, K. L., Handa, R. J., & Gonzales, R. J. (2010, Spring). Dihydrotestosterone attenuates HIF-1alpha and COX-2 in cerebral arteries following hypoxia.. Experimental Biology.
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  Anaheim, CA
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2007, Spring). Dihydrotestosterone differentially affects cerebral vascular inflammation in normoxia and hypoxia.. Experimental Biology.
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2005, Spring). Chronic dihydrotestosterone treatment on vascular function in the cerebral circulation in male rats.. Experimental Biology.
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  San Diego, CA
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2005, Spring). Gonadal hormones modulate LPS-induced inflammatory markers in rat cerebral blood vessels.. Mechanisms of Vasodilation and EDHF.
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  Antwerp, Belgium
• Gonzales, R. J., Razmara, A., Sunday, L., Krause, D. N., & Duckles, S. P. (2005, Spring). Gonadal hormones modulate LPS-induced inflammatory markers in rat cerebral blood vessels.. Brain 2005.
• Gonzales, R. J., Ghaffari, A. A., Krause, D. N., & Duckles, S. P. (2004, Spring). Modulation by testosterone of thromboxane synthase functions in rat middle cerebral arteries.. Experimental Biology.
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  Washington DC
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2004, Spring). Vascular effects of dihydrotestosterone in the cerebral circulation.. Neuroscience.
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  San Diego, CA
• Gonzales, R. J., Krause, D. N., & Duckles, S. P. (2002, Spring). Testosterone modulates non-nitric oxide, non-prostanoid endothelial dependent vascular responses in rat cerebral arteries.. Experimental Biology Late Breaking Abstract.
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  New Orleans, LA
• Gonzales, R. J., & Walker, B. R. (2001, Spring). Role of carbon monoxide in attenuated mesenteric vasoconstrictor reactivity following chronic hypoxia. FASEB J.
• Gonzales, R. J., Carter, R. W., & Kanagy, N. L. (2000, Spring). Laboratory Demonstration of vascular smooth muscle function using rat aortic ring segments. FASEB J.