Taben M. Hale
- Professor, Basic Medical Sciences
- Member of the Graduate Faculty
- Professor, Clinical Translational Sciences
- Professor, Internal Medicine
- Professor, Internal Medicine
- Vice Chair, Department of Basic Medical Sciences
- Associate Dean, Graduate Studies
Contact
- (602) 827-2139
- AZ Biomedical Collaborative 1, Rm. 327
- Tucson, AZ 85724
- tabenh@arizona.edu
Degrees
- Ph.D. Department of Pharmacology and Toxicology
- Queen's University, Kingston
- Mechanisms and Consequences of Regression of Vascular Structure During and After Antihypertensive Therapy
- B.S. Bachelor of Science, Life Sciences
- Queen's University of Kingston, Kingston
- Early Vascular Structural Change Induced by Inhibition of the Renin-Angiotensin System
Work Experience
- University of Montreal (2003 - 2008)
- Queen's University (2000 - 2003)
- Department of Pharmacology and Toxicology (1999 - 2003)
- Queen's University (1998 - 2003)
Awards
- Queen's Graduate Award
- 1998-2000, Spring 1998
- 3rd Place Post doc/Graduate student oral presentation Award
- Fall 2021
- Diversity Scholarship Award
- American Physiological Society, Fall 2021
- Cancer Center Research Day - First Prize Undergraduate Poster Competition
- Summer 2021
- International Society for Heart Research North American Section Travel Award
- ISHR, Summer 2021
- American Heart Association Research Leaders Academy
- American Heart Association, Fall 2019
- Women Achievers of Arizona
- Arizona Capital Times, Fall 2019
- Abstract Award
- Sexual Medicine Society of North America, Fall 2016
- Travel Award
- American Physiological Society: Cardiovascular, Renal Metabolic Diseases: Gender Physiology, Winter 2015
- International Society of Hypertension, Berlin, Germany, Spring 2008
- International Society of Hypertension, Prague, Czech Republic, Spring 2002
- International Society of Hypertension, Spring 2000
- Fellow of the American Heart Association
- American Heart Association, Summer 2014
- Post Doctoral Fellowship
- Heart & Stroke Foundation of Canada2006-2008, Spring 2006
- Fonds de la Recerche en Sant Qubec(Declined), Spring 2004
- Heart & Stroke Foundation of Canada(Declined), Spring 2004
- National Sciences and Engineering Research Council, 2004-2006, Spring 2004
- Groupe de Recherche sur le Systeme eux Autonome, 2003-2004, Spring 2003
- Postdoctoral Fellowship
- CHS/CIHR, Spring 2004
- Oral Presentation Award
- Canadian Hypertension Society, Fall 2003
- Ontario Hypertension Society, Spring 2003
- Merck Pharmacology Research Day, Fall 2002
- Ontario Hypertension Society, Spring 2002
- Canadian Hypertension Society Annual Meeting, Spring 2001
- Ontario Hypertension Society, Spring 2000
- Queen's Faculty of Health Sciences Research Day, Spring 2000
- Doctoral Award
- Canadian Institutes for Health Research2002-2003, Spring 2002
- Canadian Hypertensive Society/Pfizer/CIHR 2001-2002, Spring 2001
- Austin Doyle Award
- International Society of Hypertension, Spring 2000 (Award Nominee)
- Ontario Graduate Scholarship
- 2000-2001, Spring 2000
Interests
Teaching
Pharmacology, Cardiovascular and Reproductive Physiology
Research
Cardiovascular disease; Diseases of development and aging; Cardiac and vascular biology; Sexual function and dysfunction; Autonomic function; Heart Failure; End organ damage; Fibrosis; Hypertension
Courses
2024-25 Courses
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Dissertation
CTS 920 (Fall 2024)
2023-24 Courses
-
Research
CTS 900 (Spring 2024) -
Cellular Molecular& Neural Bio
CTS 555 (Fall 2023) -
Dissertation
CTS 920 (Fall 2023) -
Research
CTS 900 (Fall 2023)
2022-23 Courses
-
Dissertation
CTS 920 (Spring 2023) -
Cellular Molecular& Neural Bio
CTS 555 (Fall 2022)
2021-22 Courses
-
Dissertation
CTS 920 (Spring 2022) -
BMS Journal Colloquium
CTS 595 (Fall 2021) -
Cellular Molecular& Neural Bio
CTS 555 (Fall 2021) -
Dissertation
CTS 920 (Fall 2021)
2020-21 Courses
-
BMS Journal Colloquium
CTS 595 (Spring 2021) -
Dissertation
CTS 920 (Spring 2021) -
BMS Journal Colloquium
CTS 595 (Fall 2020) -
Cellular Molecular& Neural Bio
CTS 555 (Fall 2020) -
Dissertation
CTS 920 (Fall 2020)
2019-20 Courses
-
BMS Journal Colloquium
CTS 595 (Spring 2020) -
Dissertation
CTS 920 (Spring 2020) -
Thesis
CMM 910 (Spring 2020) -
BMS Journal Colloquium
CTS 595 (Fall 2019) -
Cellular Molecular& Neural Bio
CTS 555 (Fall 2019) -
Dissertation
CTS 920 (Fall 2019)
2018-19 Courses
-
BMS Journal Colloquium
CTS 595 (Spring 2019) -
Individualized Science Writing
CTS 585 (Spring 2019) -
Research
CTS 900 (Spring 2019) -
BMS Journal Colloquium
CTS 595 (Fall 2018) -
Cellular Molecular& Neural Bio
CTS 555 (Fall 2018) -
Research
CTS 900 (Fall 2018)
2017-18 Courses
-
BMS Journal Colloquium
CTS 595 (Spring 2018) -
BMS Journal Colloquium
CTS 595 (Fall 2017) -
Research
CTS 900 (Fall 2017)
Scholarly Contributions
Journals/Publications
- Czubryt, M. P., & Hale, T. M. (2021). Cardiac fibrosis: Pathobiology and therapeutic targets. Cellular signalling, 85, 110066.More infoCardiac fibrosis is characteristic of the end stage in nearly all forms of heart disease. Accumulation of extracellular matrix in the myocardium leads to increased risk of arrhythmia and impaired cardiac function, and ultimately progression to heart failure. Despite the critical need to slow or reverse development of cardiac fibrosis to maintain cardiac function, there are no approved therapies that directly target the extracellular matrix. Research into the underlying causes and therapeutic targets has been hampered, in part, by the lack of a clear marker for cardiac fibroblasts - the cells responsible for regulating extracellular matrix turnover. Lineage tracing studies as well as single-cell RNA sequencing studies have provided new insights into cardiac fibroblast origins and heterogeneity. Moreover, a greater understanding of pathways governing fibroblast activation during ischemic and non-ischemic cardiac remodeling and their communication with other inflammatory and cardiac cells may lead to novel therapeutic targets to slow or reverse fibrotic remodeling. The special issue of Cellular Signaling entitled "Cardiac Fibrosis: Pathobiology and Therapeutic Targets" is comprised of review articles in which these topics, as well as important open questions for future investigation, are discussed.
- Garvin, A. M., & Hale, T. M. (2021). Fibroblast shifts in the hypertensive heart: How single cell RNA-sequencing will accelerate advancements in anti-fibrotic therapies. Journal of molecular and cellular cardiology, 151, 44-45.
- Garvin, A. M., De Both, M. D., Talboom, J. S., Lindsey, M. L., Huentelman, M. J., & Hale, T. M. (2021). Transient ACE (Angiotensin-Converting Enzyme) Inhibition Suppresses Future Fibrogenic Capacity and Heterogeneity of Cardiac Fibroblast Subpopulations. Hypertension (Dallas, Tex. : 1979), 77(3), 904-918.More infoTransient ACE (angiotensin-converting enzyme) inhibition in spontaneously hypertensive rats is known to protect against future injury-induced cardiac inflammation, fibrosis, and dysfunction; however, the mechanisms of protection have not been delineated. Here, we used single-cell RNA sequencing to test the hypothesis that transient ACE inhibitor treatment would induce a persistent shift in cardiac fibroblast subpopulations. Adult male spontaneously hypertensive rats (11 weeks old, hypertensive with cardiac hypertrophy) were treated for 2 weeks with an ACE inhibitor, enalapril (30 mg/kg per day, PO), or water (untreated spontaneously hypertensive rats) followed by a 2-week washout period (n=7/group). Cardiac fibroblasts were isolated from the left ventricle and subjected to single-cell RNA sequencing. Nine clusters of fibroblasts were identified, with 98% of cells in clusters 0 to 6. The transient treatment produced significant changes both within and across clusters. Cluster 1 depicted a highly fibrogenic gene profile, with cluster 6 serving as a gateway to cluster 1. Transient ACE inhibition depleted the gateway and expanded cluster 0, which was the least fibrogenic profile. Moreover, within cluster 1 fibroblasts, ACE inhibition reduced expression of individual fibrosis genes (eg, , and ; all
- Garvin, A. M., Khokhar, B. S., Czubryt, M. P., & Hale, T. M. (2021). RAS inhibition in resident fibroblast biology. Cellular signalling, 80, 109903.More infoAngiotensin II (Ang II) is a primary mediator of profibrotic signaling in the heart and more specifically, the cardiac fibroblast. Ang II-mediated cardiomyocyte hypertrophy in combination with cardiac fibroblast proliferation, activation, and extracellular matrix production compromise cardiac function and increase mortality in humans. Profibrotic actions of Ang II are mediated by increasing production of fibrogenic mediators (e.g. transforming growth factor beta, scleraxis, osteopontin, and periostin), recruitment of immune cells, and via increased reactive oxygen species generation. Drugs that inhibit Ang II production or action, collectively referred to as renin angiotensin system (RAS) inhibitors, are first line therapeutics for heart failure. Moreover, transient RAS inhibition has been found to persistently alter hypertensive cardiac fibroblast responses to injury providing a useful tool to identify novel therapeutic targets. This review summarizes the profibrotic actions of Ang II and the known impact of RAS inhibition on cardiac fibroblast phenotype and cardiac remodeling.
- Sheng, J. A., Tan, S. M., Hale, T. M., & Handa, R. J. (2021). Androgens and Their Role in Regulating Sex Differences in the Hypothalamic/Pituitary/Adrenal Axis Stress Response and Stress-Related Behaviors. Androgens: clinical research and therapeutics, 2(1), 261-274.More infoAndrogens play a pivotal role during development. These gonadal hormones and their receptors exert organizational actions that shape brain morphology in regions controlling the stress regulatory systems in a male-specific manner. Specifically, androgens drive sex differences in the hypothalamic/pituitary/adrenal (HPA) axis and corresponding hypothalamic neuropeptides. While studies have examined the role of estradiol and its receptors in sex differences in the HPA axis and associated behaviors, the role of androgens remains far less studied. Androgens are generally thought to modulate the HPA axis through the activation of androgen receptors (ARs). They can also impact the HPA axis through reduction to estrogenic metabolites that can bind estrogen receptors in the brain and periphery. Such regulation of the HPA axis stress response by androgens can often result in sex-biased risk factors for stress-related disorders, such as anxiety and depression. This review focuses on the biosynthesis pathways and molecular actions of androgens and their nuclear receptors. The impact of androgens on hypothalamic neuropeptide systems (corticotropin-releasing hormone, arginine vasopressin, oxytocin, dopamine, and serotonin) that control the stress response and stress-related disorders is discussed. Finally, this review discusses potential therapeutics involving androgens (androgen replacement therapies, selective AR modulator therapies) and ongoing clinical trials.
- AlQudah, M., Hale, T. M., & Czubryt, M. P. (2020). Targeting the renin-angiotensin-aldosterone system in fibrosis. Matrix biology : journal of the International Society for Matrix Biology, 91-92, 92-108.More infoFibrosis is characterized by excessive deposition of extracellular matrix components such as collagen in tissues or organs. Fibrosis can develop in the heart, kidneys, liver, skin or any other body organ in response to injury or maladaptive reparative processes, reducing overall function and leading eventually to organ failure. A variety of cellular and molecular signaling mechanisms are involved in the pathogenesis of fibrosis. The renin-angiotensin-aldosterone system (RAAS) interacts with the potent Transforming Growth Factor β (TGFβ) pro-fibrotic pathway to mediate fibrosis in many cell and tissue types. RAAS consists of both classical and alternative pathways, which act to potentiate or antagonize fibrotic signaling mechanisms, respectively. This review provides an overview of recent literature describing the roles of RAAS in the pathogenesis of fibrosis, particularly in the liver, heart, kidney and skin, and with a focus on RAAS interactions with TGFβ signaling. Targeting RAAS to combat fibrosis represents a promising therapeutic approach, particularly given the lack of strategies for treating fibrosis as its own entity, thus animal and clinical studies to examine the impact of natural and synthetic substances to alter RAAS signaling as a means to treat fibrosis are reviewed as well.
- Carroll, C. C., Patel, S. H., Simmons, J., Gordon, B. D., Olson, J. F., Chemelewski, K., Saw, S., Hale, T. M., Howden, R., & Sabbaghi, A. (2020). The Impact of Genistein Supplementation on Tendon Functional Properties and Gene Expression in Estrogen-Deficient Rats. Journal of medicinal food, 23(12), 1266-1274.More infoTendinopathy risk increases with menopause. The phytoestrogen genistein prevents collagen loss during estrogen deficiency (ovariectomy [OVX]). The influence of genistein on tendon function and extracellular matrix (ECM) regulation is not well known. We determined the impact of genistein on tendon function and the expression of several genes important for the regulation of tendon ECM. Eight-week-old rats ( = 42) were divided into three groups: intact, OVX, or OVX-genistein (6 mg/kg/day) for 6 weeks. Tail fascicles were assessed with a Deben tensile stage. Achilles tendon mRNA expression was determined with digital droplet polymerase chain reaction. Compared to intact, fascicle stress tended to be lower in untreated OVX rats ( = .022). Furthermore, fascicle modulus and energy density were greater in genistein-treated rats ( .05). Compared to intact, and expression were greater and and expression were lower in OVX rats ( .05). Our findings demonstrate that genistein improves tendon function in estrogen-deficient rats. The effect of genistein was predominately on genes related to cell proliferation rather than collagen remodeling.
- Sheng, J. A., Bales, N. J., Myers, S. A., Bautista, A. I., Roueinfar, M., Hale, T. M., & Handa, R. J. (2020). The Hypothalamic-Pituitary-Adrenal Axis: Development, Programming Actions of Hormones, and Maternal-Fetal Interactions. Frontiers in behavioral neuroscience, 14, 601939.More infoThe hypothalamic-pituitary-adrenal axis is a complex system of neuroendocrine pathways and feedback loops that function to maintain physiological homeostasis. Abnormal development of the hypothalamic-pituitary-adrenal (HPA) axis can further result in long-term alterations in neuropeptide and neurotransmitter synthesis in the central nervous system, as well as glucocorticoid hormone synthesis in the periphery. Together, these changes can potentially lead to a disruption in neuroendocrine, behavioral, autonomic, and metabolic functions in adulthood. In this review, we will discuss the regulation of the HPA axis and its development. We will also examine the maternal-fetal hypothalamic-pituitary-adrenal axis and disruption of the normal fetal environment which becomes a major risk factor for many neurodevelopmental pathologies in adulthood, such as major depressive disorder, anxiety, schizophrenia, and others.
- D'Lugos, A. C., Fry, C. S., Ormsby, J. C., Sweeney, K. R., Brightwell, C. R., Hale, T. M., Gonzales, R. J., Angadi, S. S., Carroll, C. C., & Dickinson, J. M. (2019). Chronic doxorubicin administration impacts satellite cell and capillary abundance in a muscle-specific manner. Physiological reports, 7(7), e14052.More infoAnthracycline chemotherapies are effective at reducing disease recurrence and mortality in cancer patients. However, these drugs also contribute to skeletal muscle wasting and dysfunction. The purpose of this study was to assess the impact of chronic doxorubicin (DOX) administration on satellite cell and capillary densities in different skeletal muscles. We hypothesized that DOX would reduce satellite cell and capillary densities of the soleus (SOL) and extensor digitorum longus (EDL) muscles, along with muscle fiber size. Ovariectomized female Sprague-Dawley rats were randomized to receive three bi-weekly intraperitoneal injections of DOX (4 mg∙kg ; cumulative dose 12 mg∙kg ) or vehicle (VEH; saline). Animals were euthanized 5d following the last injection and the SOL and EDL were dissected and prepared for immunohistochemical and RT-qPCR analyses. Relative to VEH, CSA of the SOL and EDL fibers were 26% and 33% smaller, respectively, in DOX (P 0.05). In the SOL, MYF5 mRNA expression was increased in DOX (P
- Goldstein, J. M., Hale, T., Foster, S. L., Tobet, S. A., & Handa, R. J. (2019). Sex differences in major depression and comorbidity of cardiometabolic disorders: impact of prenatal stress and immune exposures. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(1), 59-70.More infoMajor depressive disorder topped ischemic heart disease as the number one cause of disability worldwide in 2012, and women have twice the risk of men. Further, the comorbidity of depression and cardiometabolic disorders will be one of the primary causes of disability worldwide by 2020, with women at twice the risk. Thus, understanding the sex-dependent comorbidities has public health consequences worldwide. We propose here that sex differences in MDD-cardiometabolic comorbidity originate, in part, from pathogenic processes initiated in fetal development that involve sex differences in shared pathophysiology between the brain, the vascular system, the CNS control of the heart and associated hormonal, immune, and metabolic physiology. Pathways implicate neurotrophic and angiogenic growth factors, gonadal hormone receptors, and neurotransmitters such as gamma amino butyric acid (GABA) on neuronal and vascular development of HPA axis regions, such as the paraventricular nucleus (PVN), in addition to blood pressure, in part through the renin-angiotensin system, and insulin and glucose metabolism. We show that the same prenatal exposures have consequences for sex differences across multiple organ systems that, in part, share common pathophysiology. Thus, we believe that applying a sex differences lens to understanding shared biologic substrates underlying these comorbidities will provide novel insights into the development of sex-dependent therapeutics. Further, taking a lifespan perspective beginning in fetal development provides the opportunity to target abnormalities early in the natural history of these disorders in a sex-dependent way.
- Hale, T. M., & Lindsey, M. L. (2019). Connecting the Dots for Connective Tissue Growth Factor Roles in Cardiac Wound Healing After Myocardial Infarction. JACC. Basic to translational science, 4(1), 95-97.
- Willeman, M. N., Chawla, M. K., Zempare, M. A., Biwer, L. A., Hoang, L. T., Uprety, A. R., Fitzhugh, M. C., De Both, M., Coleman, P. D., Trouard, T. P., Alexander, G. E., Mitchell, K. D., Barnes, C. A., Hale, T. M., & Huentelman, M. (2019). Gradual hypertension induction in middle-aged Cyp1a1-Ren2 transgenic rats produces significant impairments in spatial learning. Physiological reports, 7(6), e14010.More infoHypertension is a major health concern in the developed world, and its prevalence increases with advancing age. The impact of hypertension on the function of the renal and cardiovascular systems is well studied; however, its influence on the brain regions important for cognition has garnered less attention. We utilized the Cyp1a1-Ren2 xenobiotic-inducible transgenic rat model to mimic both the age of onset and rate of induction of hypertension observed in humans. Male, 15-month-old transgenic rats were fed 0.15% indole-3-carbinol (I3C) chow to slowly induce renin-dependent hypertension over a 6-week period. Systolic blood pressure significantly increased, eventually reaching 200 mmHg by the end of the study period. In contrast, transgenic rats fed a control diet without I3C did not show significant changes in blood pressure (145 mmHg at the end of study). Hypertension was associated with cardiac, aortic, and renal hypertrophy as well as increased collagen deposition in the left ventricle and kidney of the I3C-treated rats. Additionally, rats with hypertension showed reduced savings from prior spatial memory training when tested on the hippocampus-dependent Morris swim task. Motor and sensory functions were found to be unaffected by induction of hypertension. Taken together, these data indicate a profound effect of hypertension not only on the cardiovascular-renal axis but also on brain systems critically important for learning and memory. Future use of this model and approach may empower a more accurate investigation of the influence of aging on the systems responsible for cardiovascular, renal, and neurological health.
- 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.More infoThis 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.
- Potter, R. M., Huynh, R. T., Volper, B. D., Arthur, K. A., D'Lugos, A. C., Sørensen, M. A., Magnusson, S. P., Dickinson, J. M., Hale, T. M., & Carroll, C. C. (2017). Impact of TGF-β inhibition during acute exercise on Achilles tendon extracellular matrix. American journal of physiology. Regulatory, integrative and comparative physiology, 312(1), R157-R164.More infoThe purpose of this study was to evaluate the role of TGF-β1 in regulating tendon extracellular matrix after acute exercise. Wistar rats exercised (n = 15) on a treadmill for four consecutive days (60 min/day) or maintained normal cage activity. After each exercise bout, the peritendinous space of each Achilles tendon was injected with a TGF-β1 receptor inhibitor or sham. Independent of group, tendons injected with inhibitor exhibited ~50% lower Smad 3 (Ser423/425) (P < 0.05) and 2.5-fold greater ERK1/2 phosphorylation (P < 0.05) when compared with sham (P < 0.05). Injection of the inhibitor did not alter collagen content in either group (P > 0.05). In exercised rats, hydroxylyslpyridinoline content and collagen III expression were lower (P < 0.05) in tendons injected with inhibitor when compared with sham. In nonexercised rats, collagen I and lysyl oxidase (LOX) expression was lower (P < 0.05) in tendons injected with inhibitor when compared with sham. Decorin expression was not altered by inhibitor in either group (P > 0.05). On the basis of evaluation of hematoxylin and eosin (H&E) stained cross sections, cell numbers were not altered by inhibitor treatment in either group (P > 0.05). Evaluation of H&E-stained sections revealed no effect of inhibitor on collagen fibril morphology. In contrast, scores for regional variation in cellularity decreased in exercised rats (P < 0.05). No differences in fiber arrangement, structure, and nuclei form were noted in either group (P > 0.05). Our findings suggest that TGF-β1 signaling is necessary for the regulation of tendon cross-link formation, as well as collagen and LOX gene transcription in an exercise-dependent manner.
- Goldstein, J. M., Holsen, L., Huang, G., Hammond, B. D., James-Todd, T., Cherkerzian, S., Hale, T. M., & Handa, R. J. (2016). Prenatal stress-immune programming of sex differences in comorbidity of depression and obesity/metabolic syndrome. Dialogues in clinical neuroscience, 18(4), 425-436.More infoMajor depressive disorder (MDD) is the number one cause of disability worldwide and is comorbid with many chronic diseases, including obesity/metabolic syndrome (MetS). Women have twice as much risk for MDD and comorbidity with obesity/MetS as men, although pathways for understanding this association remain unclear. On the basis of clinical and preclinical studies, we argue that prenatal maternal stress (ie, excess glucocorticoid expression and associated immune responses) that occurs during the sexual differentiation of the fetal brain has sex-dependent effects on brain development within highly sexually dimorphic regions that regulate mood, stress, metabolic function, the autonomic nervous system, and the vasculature. Furthermore, these effects have lifelong consequences for shared sex-dependent risk of MDD and obesity/MetS. Thus, we propose that there are shared biologic substrates at the anatomical, molecular, and/or genetic levels that produce the comorbid risk for MDD-MetS through sex-dependent fetal origins.
- Biwer, L. A., D'souza, K. M., Abidali, A., Tu, D., Siniard, A. L., DeBoth, M., Huentelman, M., & Hale, T. M. (2016). Time course of cardiac inflammation during nitric oxide synthase inhibition in SHR: impact of prior transient ACE inhibition. Hypertension research : official journal of the Japanese Society of Hypertension, 39(1), 8-18.More infoWe have previously demonstrated that angiotensin-converting enzyme (ACE) inhibition with enalapril produces persistent effects that protect against future nitric oxide synthase (NOS) inhibitor (l-arginine methyl ester, l-NAME)-induced cardiac dysfunction and outer wall collagen deposition in spontaneously hypertensive rats (SHR). In the present study, we dissect the cytokine/chemokine release profile during NOS inhibition, its correlation to pathological cardiac remodeling and the impact of transient ACE inhibition on these effects. Adult male SHR were treated with enalapril (E+L) or tap water (C+L) for 2 weeks followed by a 2-week washout period. Rats were then subjected to 0, 3, 7 or 10 days of l-NAME treatment. The temporal response to NOS inhibition was evaluated by measuring arterial pressure, cardiac remodeling and cytokine/chemokine levels. l-NAME equivalently increased blood pressure and myocardial and vascular injury in C+L and E+L rats. However, pulse pressure (PP) was only transiently altered in C+L rats. The levels of several inflammatory mediators were increased during l-NAME treatment. However, interleukin-6 (IL-6) and IL-10 and monocyte chemoattractant protein-1 were uniquely increased in C+L hearts; whereas IL-4 and fractalkine were only elevated in E+L hearts. By days 7 and 10 of l-NAME treatment, there was a significant increase in the cardiac density of macrophages and proliferating cells, respectively only in C+L rats. Although myocardial injury was similar in both treatment groups, PP was not changed and there was a distinct cardiac chemokine/cytokine signature in rats previously treated with enalapril that may be related to the lack of proliferative response and macrophage infiltration in these hearts.
- D'Souza, K. M., Biwer, L. A., Madhavpeddi, L., Ramaiah, P., Shahid, W., & Hale, T. M. (2015). Persistent Change in Cardiac Fibroblast Physiology Following Transient ACE Inhibition. American journal of physiology. Heart and circulatory physiology, ajpheart.00615.2015.More infoTransient angiotensin converting enzyme (ACE) inhibition induces persistent changes that protect against future nitric oxide synthase (NOS) inhibitor-induced cardiac fibrosis and inflammation. Given the role of fibroblasts in mediating these effects, the present study investigates whether prior ACE inhibition produced persistent changes in cardiac fibroblast physiology. Adult male spontaneously hypertensive rats (SHR) were treated with vehicle (C+L) or the ACE inhibitor, enalapril (E+L) for 2 weeks followed by a 2-week washout period, and a subsequent 7-day challenge with the NOS inhibitor, L-NAME. A third set of untreated SHR served as control. At the end of the study period, cardiac fibroblasts were isolated from control, C+L, and E+L left ventricles to assess proliferation rate, collagen expression, and chemokine release in vitro. After 7 days of NOS inhibition there were areas of myocardial injury, but no significant change in collagen deposition in E+L and C+L hearts in vivo. In vitro, cardiac fibroblasts isolated from C+L, but not E+L, were hyperproliferative, demonstrated increased collagen I gene expression, and an elevated secretion of the macrophage-recruiting chemokines, monocyte chemoattractant protein-1 and granulocyte macrophage-colony stimulating factor. These findings demonstrate that in vivo L-NAME treatment produces phenotypic changes in fibroblasts that persist in vitro. Moreover, this is the first demonstration that transient ACE inhibition can produce a persistent modification of cardiac fibroblast phenotype to one that is less inflammatory and fibrogenic. It may be that the cardio-protective effects of ACE inhibition are related in part to beneficial changes in the cardiac fibroblast physiology.
- Hale, T. M. (2015). Persistent phenotypic shift in cardiac fibroblasts: impact of transient renin angiotensin system inhibition. Journal of molecular and cellular cardiology.More infoFibrotic cardiac remodeling ultimately leads to heart failure - a debilitating and costly condition. Select antihypertensive agents have been effective in reducing or slowing the development of cardiac fibrosis. Moreover, some experimental studies have shown that the reduction in fibrosis induced by these agents persists long after stopping treatment. What has not been as well investigated is whether this transient treatment results in a protection against future fibrotic cardiac remodeling. In the present review, previously published studies are re-examined to assess whether the relative percent increase in collagen deposition over an off-treatment period is attenuated, relative to control, following transient antihypertensive treatment in young or adult rats. Present findings suggest that transient inhibition of the renin angiotensin system (RAS) not only produces a sustained reduction in cardiac fibrosis, but also results in a degree of protection against future collagen deposition. In addition, prior transient RAS inhibition appears to alter the cardiac fibroblast phenotype such that these cells show a muted response to myocardial injury - namely reduced proliferation, chemokine release, and collagen deposition. This review puts forth several potential mechanisms underlying this long-term cardiac protection that is afforded by transient RAS inhibition. Specifically, fibroblast phenotypic change, cardiac fibroblast apoptosis, sustained suppression of the RAS, persistent reduction in left ventricular hypertrophy, and persistent reduction in arterial pressure are each discussed. Identifying the mechanisms ultimately responsible for this change in cardiac fibroblast response to injury, hypertension, and aging may reveal novel targets for therapy.
- Volper, B. D., Huynh, R. T., Arthur, K. A., Noone, J., Gordon, B. D., Zacherle, E. W., Munoz, E., Sørensen, M. A., Svensson, R. B., Broderick, T. L., Magnusson, S. P., Howden, R., Hale, T. M., & Carroll, C. C. (2015). The influence of acute and chronic streptozotocin-induced diabetes on rat tendon extracellular matrix and mechanical properties. American journal of physiology. Regulatory, integrative and comparative physiology, ajpregu.00189.2015.More infoDiabetes is a major risk factor for tendinopathy and tendon abnormalities are common in diabetic patients. The purpose of this study was to evaluate the effect of streptozotocin-induced (STZ, 60 mg⋅kg(-1)) diabetes and insulin therapy on tendon mechanical and cellular properties. Sprague Dawley rats (n=40) were divided into four groups: non-diabetic (Control), 1-week of diabetes (Acute), 10 weeks of diabetes (Chronic), 10 weeks of diabetes with insulin (Insulin). After ten weeks Achilles tendon and tail fascicle mechanical properties were similar between groups (p>0.05). Cell density in the Achilles was greater in the Chronic group when compared to Control and Acute (p
- Hale, T. M. (2014). NQO1 activation: a novel antihypertensive treatment strategy?. Journal of hypertension, 32(2), 233-5.
- Biwer, L. A., Broderick, T. L., Xu, H., Carroll, C., & Hale, T. -. (2013). Short-Term ACE Inhibition Produces Long-Term Protection Against NOS Inhibitor-Induced Cardiac Dysfunction. Acta Physiologica, 1(207), 156-165.More infoPMID: 22834875
- Biwer, L. A., Broderick, T. L., Xu, H., Carroll, C., & Hale, T. M. (2013). Protection against L-NAME-induced reduction in cardiac output persists even after cessation of angiotensin-converting enzyme inhibitor treatment. Acta physiologica (Oxford, England), 207(1), 156-65.More infoWe have demonstrated that short-term angiotensin-converting enzyme (ACE) inhibition in adult spontaneously hypertensive rats produces cardiac changes that persist following cessation of treatment that result in a reduced inflammatory, proliferative and fibrotic response to the nitric oxide synthase inhibitor N(ω) -Nitro-l-arginine methyl ester (L-NAME). The present study examines whether prior ACE inhibition with enalapril also protects against L-NAME-induced cardiac dysfunction.
- Der Sarkissian, S., Tea, B., Touyz, R. M., deBlois, D., & Hale, T. M. (2013). Role of angiotensin II type 2 receptor during regression of cardiac hypertrophy in spontaneously hypertensive rats. Journal of the American Society of Hypertension : JASH, 7(2).More infoWe previously reported that the AT1 receptor antagonist valsartan and the angiotensin converting enzyme (ACE) inhibitor enalapril decrease DNA synthesis and stimulate apoptosis in interstitial fibroblasts and epicardial mesothelial cells during regression of ventricular hypertrophy in spontaneously hypertensive rats (SHR). To examine the role of the AT2 receptor in this model, we studied hearts from SHR treated with valsartan or enalapril either alone or combined with the AT2 antagonist PD123319 for 1 or 2 weeks. Apoptosis was evaluated by quantification of DNA fragmentation or by TUNEL labeling. At 1 week, valsartan significantly increased ventricular DNA fragmentation, increased apoptosis in epicardial mesothelial cells, and decreased DNA synthesis. At 2 weeks, ventricular DNA content and cardiomyocyte cross-sectional area were significantly reduced. These valsartan-induced changes were attenuated by PD123319 co-administration. However, valsartan-induced increases in apoptosis of left ventricular interstitial non-cardiomyocytes was unaffected by the AT2 blocker. Enalapril-induced changes were similar to those observed with valsartan but were not affected by co-treatment with PD123319. These results demonstrate that AT1 and AT2 receptors act in a coordinated yet cell-specific manner to regulate cell growth and apoptosis in the left ventricle of SHR during AT1 receptor blockade but not ACE inhibition.
- Hale, T. M., Robertson, S. J., Burns, K. D., & deBlois, D. (2012). Short-term ACE inhibition confers long-term protection against target organ damage. Hypertension research : official journal of the Japanese Society of Hypertension, 35(6).More infoAngiotensin converting enzyme (ACE) inhibitors reduce left ventricular (LV) hypertrophy and cardiovascular-renal fibrosis. Experimentally, changes in the LV and kidney persist even after cessation of treatment. The present study investigates whether brief ACE inhibition in spontaneously hypertensive rats (SHR) provides long-term protection against the LV and kidney damage induced by the nitric oxide synthase inhibitor N-ω-nitro-L-arginine-methyl ester (L-NAME). SHR received the ACE inhibitor enalapril (n = 36) or tap water (n = 36). In all, 12 control and treated SHR were sacrificed after 2 weeks and remaining rats were taken off-treatment. After a 2-week washout, 12 controls or previously treated SHR were sacrificed and remaining rats were treated with L-NAME ((control (Con)+L, enalapril (Enal)+L) for 10 days. At sacrifice, blood pressure was recorded via carotid artery cannulation in anesthetized rats, and blood, the kidney and LV were isolated for analysis. LV mass and arterial pressure were significantly reduced by enalapril. LV mass showed a persistent reduction throughout the study. In LV, prior enalapril treatment provided significant (P
- Doyon, M., Hale, T. -., Huot-Marchand, J. E., Wu, R., deChamplain, J., & deBlois, D. (2011). Does Atorvastatin Induce Aortic Smooth Muscle Cell Apoptosis In Vivo?. Vascular Pharmacology, 1(54), 5-12.More infoPMID: 20951229
- Hale, T. M., Bushfield, T. L., Woolard, J., Pang, J. J., Rees-Milton, K. J., & Adams, M. A. (2011). Changes critical to persistent lowering of arterial pressure in spontaneously hypertensive rat occur early in antihypertensive treatment. Journal of hypertension, 29(1).More infoAngiotensin-converting enzyme inhibition (ACEI) in adult spontaneously hypertensive rats (SHRs) produces reductions in mean arterial pressure (MAP) and vascular structure that persist after treatment cessation. This study used an intermittent treatment strategy to determine the time course of changes in MAP, vascular resistance properties, and the tissue levels of endothelin.
- Hale, T. M., Hannan, J. L., Carrier, S., deBlois, D., & Adams, M. A. (2009). Targeting vascular structure for the treatment of sexual dysfunction. The journal of sexual medicine, 6 Suppl 3.More infoErectile dysfunction (ED) and cardiovascular disease often coexist and have many common risk factors. In hypertension, the structure of blood vessels is modified such that there is an increase in medial wall thickness relative to lumen size. Certain antihypertensive agents have been found to induce a regression of vascular structure such that a "hypertensive" vessel appears phenotypically more like that from a normotensive.
- Lemay, J., Hale, T. M., & deBlois, D. (2009). Neointimal-specific induction of apoptosis by losartan results in regression of vascular lesion in rat aorta. European journal of pharmacology, 618(1-3).More infoWe previously reported that initiating treatment with the angiotensin II receptor antagonist losartan, prior to and immediately after balloon injury, attenuates neointimal hyperplasia via induction of smooth muscle cell (SMC) apoptosis in the aorta of spontaneously hypertensive rats (SHR). The present study examines whether losartan can induce regression of an established neointima. Balloon angioplasty was performed in the aorta of 1 1 week-old SHR. Five weeks were allowed for neointima formation before rats received placebo or losartan (30 mg/kg/day) for 1 to 4 weeks. Blood pressure was measured by tail cuff plethysmography. Losartan significantly reduced blood pressure (16%) versus placebo within 2 weeks of treatment. In situ labeling with terminal deoxynucleotidyl transferase among neointimal SMC was transiently increased with losartan (10-fold at 2 weeks; P=0.004) in correlation with internucleosomal fragmentation of vascular DNA. Accordingly, losartan reversed neointimal hyperplasia by 43% (P=0.002) and 61% (P=0.007) at weeks 2 and 4, respectively, and neointimal mass by 63% (P
- Beharry, R. K., Hale, T. M., Heaton, J. P., Shamloul, R., & Adams, M. A. (2008). Restoration of female genital vasocongestive arousal responses in young and aged rats. The journal of sexual medicine, 5(4).More infoTreatments of aged, male hypertensive rats that induce vascular remodeling or that normalize endothelial function are known to produce sustained improvements in erectile function. Whether the treatments targeting these processes benefit female genital vasocongestive arousal (GVA) responses is currently not known.
- Jomphe, C., Gabriac, M., Hale, T. M., Héroux, L., Trudeau, L., Deblois, D., Montell, E., Vergés, J., & du Souich, P. (2008). Chondroitin sulfate inhibits the nuclear translocation of nuclear factor-kappaB in interleukin-1beta-stimulated chondrocytes. Basic & clinical pharmacology & toxicology, 102(1).More infoChondroitin sulfate is referred as a symptomatic slow-acting drug for osteoarthritis because it improves articular function, and reduces joint swelling and effusion. In addition, chondroitin sulfate prevents joint space narrowing of the knee. We hypothesized that the anti-inflammatory effect of chondroitin sulfate is associated to a decrease in the activation of mitogen-activated protein kinases (MAPK) and of the transcription factors nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). Cultured rabbit chondrocytes were stimulated with interleukin-1beta (IL-1beta) in presence of chondroitin sulfate. Nuclear translocation of NF-kappaB and AP-1, and nitrite concentrations (as an index for nitric oxide) was assessed 48 hr later. The effect of chondroitin sulfate on IL-1beta activation of extracellular signal-regulated kinase 1/2 (Erk1/2) and p38MAPK was documented by immunoblot. The effect of chondroitin sulfate on sodium nitroprusside-induced apoptosis was evaluated with the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling assay. Chondroitin sulfate reduced IL-1beta-induced NF-kappaB nuclear translocation, but not AP-1 translocation, it decreased IL-1beta-induced phosphorylation of Erk1/2 and abrogated p38MAPK phosphorylation, but did not prevent IL-1beta-induced increase in nitrite. Finally, chondroitin sulfate decreased nitroprusside-induced apoptosis of the chondrocytes. These results suggest that some of the biological activities of chondroitin sulfate may be associated to the reduction in Erk1/2 and p38MAPK phosphorylation and nuclear transactivation of NF-kappaB.
- Hannan, J. L., Smallegange, C., Hale, T. M., Heaton, J. P., & Adams, M. A. (2006). Impact of antihypertensive treatments on erectile responses in aging spontaneously hypertensive rats. Journal of hypertension, 24(1).More infoWe previously demonstrated that brief, aggressive antihypertensive therapy recovered erectile function in 40-week-old spontaneously hypertensive rats (SHR). The present study examined the impact of antihypertensive and testosterone treatments on erectile function in aging SHR.
- Hale, T. -., Hannan, J. L., Heaton, J. W., & Adams, M. A. (2005). Common Therapeutic Strategies in the Management of Sexual Dysfunction and Cardiovascular Disease.. Current Drug Targets: Cardiovascular and Hematological Disorders, 2(5), 185-195.More infoPMID: 15853758
- Smallegange, C., Hale, T. M., Bushfield, T. L., & Adams, M. A. (2004). Persistent lowering of pressure by transplanting kidneys from adult spontaneously hypertensive rats treated with brief antihypertensive therapy. Hypertension, 44(1).More infoKidney function is critical in determining the level of arterial pressure and in the pathogenesis of hypertension. Important evidence comes from studies in which the level of blood pressure is dictated by the donor when kidneys are transplanted between genetically hypertensive and normotensive rats. We have hypothesized that pharmacotherapy modifies specific properties of the kidney, particularly the vasculature, such that after kidney transplantation, there are persistent changes in the level of arterial pressure. Consistent with previous studies, a 2-week aggressive treatment of adult (15 weeks) spontaneously hypertensive rats with an angiotensin-converting enzyme inhibitor (enalapril) combined with a low-salt diet induced a persistent change in the kidney and a decrease in arterial pressure (18%). These persistent changes in arterial pressure could be completely transferred to untreated adult spontaneously hypertensive rats by kidney transplantation (ie, pressure in untreated rats was decreased after transplantation of a kidney donated from a previously treated rat). Further, the importance of kidney-specific changes was demonstrated by finding that the treatment-induced lowering of arterial pressure was completely reversed by transferring an untreated kidney into a previously treated rat. The specific treatment-induced changes to the kidney included a decrease in structurally based renal vascular resistance that was similar to the persistent lowering of arterial pressure. These data provide evidence for a link between the treatment-induced changes in kidney vascular structure and the persistent lowering of arterial pressure. The findings also suggest that a key pharmacotherapeutic target in hypertension should be kidney-specific changes, such as renal vascular structure.
- Beharry, R. S., Hale, T. -., Wilson, L., Heaton, J. W., & Adams, M. A. (2003). Evidence for centrally- initiated genital vasocongestive engorgement in the female rat: findings from a new model of the female sexual arousal response.. International Journal of Impotence Research: Journal of Sexual Medicine, 2(15), 122-128.More info(Featured Article) PMID: 12789392
- Hale, T. -., Heaton, J. W., & Adams, M. A. (2003). A Framework for the Present and Future Development of Experimental Models of Female Sexual Dysfunction.. International Journal of Impotence Research: Journal of Sexual Medicine, 5(15), S75-S79.More infoPMID: 14551581
- Hale, T. M., Shoichet, M. J., Bushfield, T. L., & Adams, M. A. (2003). Time course of vascular structural changes during and after short-term antihypertensive treatment. Hypertension, 42(2).More infoThe present study characterized the persistent changes (ie, off-treatment) resulting from short-term antihypertensive treatments on mean arterial pressure (MAP) and structurally based vascular resistance. Rats were treated for 14 days with enalapril (30 mg x kg(-1) x d(-1)) with regular (ENAL, 0.4%) or low salt (ELS, 0.04%) diets, or a triple therapy (Triple: hydralazine 45 mg x kg(-1) x d(-1), hydrochlorothiazide 100 mg/L, and nifedipine 200 mg/d). MAP was continuously recorded via radiotelemetry. Structurally based hindlimb vascular resistance properties (resistance at maximum dilation [Max Dil]; resistance at maximum constriction [Max Con]) were assessed after 14-day enalapril treatment and 2 to 3 weeks after all drugs were withdrawn. Aortic urokinase plasminogen activator (uPA) activity was measured by zymography after 14 days of ELS. All treatments induced a significant, persistent decrease in the off-treatment MAP (ENAL downward arrow 12+/-4.6%, ELS downward arrow 16+/-2.6%, Triple downward arrow 5+/-4.17%). During treatment (14 days) the enalapril group had significant changes in the index of medial bulk (Max Con downward arrow 15+/-2.6%), but only minimal changes in lumen properties (Max Dil downward arrow 3+/-6.5%, NS). After stopping therapy, vascular properties at Max Dil were significantly decreased only in the 2 enalapril groups (ENAL downward arrow 15+/-7.9%, P
- Woolard, J., Hale, T. M., Bushfield, T. L., & Adams, M. A. (2003). Persistent lowering of arterial pressure after continuous and intermittent therapy. Journal of hypertension, 21(4).More infoThe present study investigates the impact of antihypertensive treatment on persistent reduction of arterial pressure after cessation of drug treatment.
- Hale, T. -., Okabe, H., Bushfield, T. L., Heaton, J. W., & Adams, M. A. (2002). Recovery of erectile function following brief, aggressive antihypertensive therapy.. Journal of Urology, 348-354.More infoPMID: 12050568
- Leary, S. C., Michaud, D., Lyons, C. N., Hale, T. -., Bushfield, T. L., Adams, M. A., & Moyes, C. D. (2002). Bioenergetic remodeling of heart during treatment of spontaneously hypertensive rats with enalapril.. American Journal of Physiology - Heart & Circulatory Physiology, 2(283), H540-8.More infoPMID: 12124199
- Hale, T. -., Okabe, H., Kumon, H., & Adams, J. W. (2001). Antihypertensive drugs induce structural remodeling in the penile vasculature.. Journal of Urology, 739-745.More infoPMID: 11458127
- Okabe, H., Hale, T. -., Kumon, H., Keaton, J. W., & Adams, M. A. (1999). The penis is not protected - in hypertension there are vascular changes in the penis which are similar to those in other vascular beds.. International Journal of Impotence Research, 133-140.
Presentations
- Ferreira, K., Garvin, A. M., Nunez, W., Singh, I., Frye, R. E., & Hale, T. (2021). Impact of Doxorubicin and Metformin on Cardiac Mitochondrial Electron Transport Chain Proteins. Arizona Physiological Society.
- Hale, T., Garvin, A. M., Floyd, D. B., & Nunez, W. S. (2021). Is Prohibitin a Mediator of Cardiac Fibroblast Activation?. Arizona Physiological Society.
- Altaf, A., Soni, P., Kim, M., Garvin, A. M., & Hale, T. (2019, November). Unlocking Signaling Mechanisms That Underlie Persistent Anti-Fibrotic Effects of Transient ACE Inhibition. Arizona Physiological Society.
- 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.
- Aziz, A., Hammond, B. D., Madhavpeddi, L., Thompson, M. K., Handa, R. J., & Hale, T. -. (2016, October). Sex Differences in Inflammatory Status of Adult Rats Prenatally Exposed to Dexamethasone. Arizona Physiological Society.More infoOral presentation
- Hale, T. -., Hammond, B. D., Thompson, M. K., Madhavpeddi, L., Goldstein, J. M., & Handa, R. J. (2016, February). Fetal Risk Factors for Adult Cardiometabolic Disorders and Comorbid Depression. ABRC and Flinn Foundation Awardee Research Conference.More infoOral presentation
- Hammond, B. D., Thompson, M. K., Madhavpeddi, L., Hale, T. -., & Handa, R. J. (2016, November). Prenatal Dexamethasone Exposure Alters the Postnatal Leptin Surge in Rats. Society for Neuroscience.More infoOral presentation
- McCormick, B. A., Hannan, J. L., Huot-Marchand, J., Carroll, C. C., Carrier, S., deBlois, D., & Hale, T. (2016, November). Bradykinin B1 Receptor Antagonism Prevents Angiotensin II-Induced Erectile Dysfunction. Sexual Medicine Society of North America.
- Royal, C., Thompson, M. K., Madhavpeddi, L., Hammond, B. D., Hale, T. -., & Handa, R. J. (2016, October). Prenatal Dexamethasone Exposure Induces a Female-Specific Alteration in the Postnatal Leptin Surge in Rat. Arizona Physiological Society.More infoOral presentation
- D'Lugos, A. C., Mahmood, T., Cosgrove, C., Dedmon, W. L., Astill, B. D., Katsma, M., Gonzales, R. J., Hale, T. -., Carroll, C. C., Angadi, S. S., & Dickinson, J. M. (2015, November). HIGH INTENSITY EXERCISE PRESERVES MYOCELLULAR SIZE THROUGHOUT DOXORUBICIN TREATMENT. Arizona Physiological SocietyAmerican Physiological Society.More infoOral presentation
- Gonzales, R. J., Raman, P., Vijayavel, N., Kerrigan, C., Echeverria, J., Dickinson, J. M., Hale, T. -., Carroll, C., & Angadi, S. S. (2015, November). Doxorubicin Reduces Proinflammatory Mediator Expression in Brain and Pial Arteries from Ovariectomized Female Rats. Cardiovascular, Renal, and Metabolic Diseases: Physiology and GenderAmerican Physiological Soceity.
- Hale, T. -., Carbone, D. E., Madhavpeddi, L., Thompson, M. K., & Handa, R. J. (2015, November). Sex Differences in Cardiovascular Responses to Stress in Adult Rats Prenatally Exposed to Dexamethasone. Arizona Physiological SocietyAmerican Physiological Society.More infoOral presentation
- Hale, T. -., Carbone, D. E., Madhavpeddi, L., Thompson, M. K., & Handa, R. J. (2015, November). Sex Differences in Cardiovascular Responses to Stress in Adult Rats Prenatally Exposed to Dexamethasone. Cardiovascular, Renal, and Metabolic Diseases: Physiology and GenderAmerican Physiological Society.More infoOral presentation
- Madhavpeddi, L., Biwer, L. A., D'Souza, K. M., & Hale, T. -. (2015, April). Persistent Phenotypic Shift in Cardiac Fibroblasts Following Transient ACE Inhibition. Experimental BiologyAmerican Society of Pharmacology & Experimental Therapeutics.More infoOral presentation
- Mahmood, T., D'Lugos, A. C., Cosgrove, C., Dedmon, W. L., Astill, B. D., Patel, S., Katsma, M., Gonzales, R. J., Hale, T. -., Carroll, C. C., Angadi, S. S., & Dickinson, J. M. (2015, November). HIGH INTENSITY EXERCISE PROTECTS SKELETAL MUSCLE FROM COMPLICATIONS OF DOXORUBICIN TREATMENT. Arizona Physiological SocietyAmerican Physiological Society.More infoOral presentation
- McCormick, B. A., Huot-Marchand, J., Carroll, C., Carrier, S., deBlois, D., & Hale, T. -. (2015, November). DIFFERENTIAL CARDIOVASCULAR AND PENILE RESPONSES TO ANGIOTENSIN II AND BRADYKININ B1- RECEPTOR ANTAGONISM TREATMENT IN SPRAGUEDAWLEY RATS. Arizona Physiological SocietyAmerican Physiological Society.More infoAward winning poster
- Hale, T. M. (2013, Summer). ACE Inhibition Produces Persistent Cardio-Protective Effects Following Cessation Of Treatment: Role Of The Cardiac Fibroblast. BMS Research Retreat.
- 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. Arizona Physiological Society. Phoenix: Arizona Physiological Society.
Poster Presentations
- Bailey, A. C., Floyd, D. B., Garvin, A. M., Nunez, W. S., & Hale, T. M. (2021). Impact of Transient ACE Inhibition on Angiotensin II-Induced Collagen Gene Expression. ABRC/Flinn Annual Research Meeting.
- Ferreira, K., Garvin, A. M., Nunez, W. S., & Hale, T. (2021). Impact of Doxorubicin and Metformin on Cardiac Electron Transport Chain. Cancer Center Research Day.
- Floyd, D. B., Garvin, A. M., Nunez, W. S., & Hale, T. M. (2021). Sex-Selective Impact of Transient ACE Inhibition on Angiotensin II-Induced Collagen Gene Expression. Experimental Biology.
- Garvin, A. M., Altaf, A., Siegel, M., Nunez, W. S., Soni, P., & Hale, T. (2021). Angiotensin II Elicits Sex-Specific Fibrogenic Responses that are Selectively Amenable to Prior ACE Inhibition. International Society of Heart Research North American Section Annual Meeting.
- Garvin, A. M., Floyd, D. B., Altaf, A., Siegel, M. M., Nunez, W. S., & Hale, T. (2021). Transient Angiotensin Converting Enzyme Inhibition Protects AgainstFuture Fibrogenic Responses Via Sex-specific Mechanisms. American Heart Association Basic Cardiovascular Sciences Annual Meeting.
- Madhavpeddi, L., Handa, R. J., & Hale, T. (2021). Gonadal Steroid Hormones Do Not Alter Stress-Induced Cardiovascular Responses in Adult Male and Female Rats Exposed to Dexamethasone In Utero. American Physiological Society New Trends in Sex and Gender Medicine.
- Madhavpeddi, L., Handa, R. J., & Hale, T. (2021). Gonadal Steroid Hormones Do Not Alter Stress-Induced Cardiovascular Responses in Adult Male and Female Rats Exposed to Dexamethasone In Utero. Arizona Physiological Society.
- Madhavpeddi, L., Handa, R. J., & Hale, T. (2021). Stress-Induced Cardiovascular Responses In Adult Male and Female Rats Exposed to Dexamethasone In Utero are Independent of Adult Gonadal Steroids. NIH/ORWH SCORE 2021 Annual Meeting Specialized Centers of Research Excellence: A U54 Program on Sex Differences.
- Garvin, A. M., Perez, O., McCormic, B. A., & Hale, T. (2019, April). Altered Antioxidant and Inflammatory Signaling by Fibroblasts in the Hypertensive Heart. Experimental Biology.
- Garvin, A. M., Talboom, J. S., DeBoth, M., Huentelman, M. J., & Hale, T. (2019, June). Heterogeneity of Cardiac Fibroblast Populations is Reduced by Transient Angiotensin Converting Enzyme Inhibition in Hypertensive Rats. American Society of Matrix Biology Workshop Fibroblasts: The Arbiters of the Extracellular Matrix Workshop.
- Garvin, A. M., Talboom, J. S., DeBoth, M., Huentelman, M. J., & Hale, T. (2019, November). Transient Angiotensin Converting Enzyme Inhibition in Hypertensive Rats Homogenizes the Cardiac Fibroblast Population Supporting a Less Fibrogenic Transcriptome. Arizona Physiological Society.
- Madhavpeddi, L., Carbone, D., Handa, R. J., & Hale, T. (2019, November). Impact of Prenatal Dexamethasone on Adult Cardiovascular Autonomic Regulation. Arizona Physiological Society.
- Madhavpeddi, L., Hammond, B. D., Hale, T., & Handa, R. J. (2019, April). Impact of Prenatal Dexamethasone on Circulating Cytokines and Chemokines in Neonatal and Adult Rats. Experimental Biology.
- Madhavpeddi, L., Hammond, B. D., Handa, R. J., & Hale, T. (2019, May). Impact of Prenatal Glucocorticoid Exposure on Central Autonomic Signaling. ABRC/Flinn Foundation Research Symposium. UACOM-P: ABRC and Flinn Foundation.
- Siegel, M. M., McCormick, B. A., Nayek, T., & Hale, T. (2019, April). Tissue Specific Impact of B1 Antagonism on Anti-Oxidant Enzyme Expression. Experimental Biology.
- Thomas, T. C., Gulati, M., Hartmark-Hill, J. R., Mallin, E., Lucio, F., Parrish, J., Muhammad, S., Nelson, L. R., Omalley, C. W., Garcia-Filion, P., Mahnert, N., Federico, G., Titelbaum, A. R., Gonzales, R. J., Herbst-Kralovetz, M., Hale, T., & Gallitano-Mendel, A. L. (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.
- Thomas, T. C., Gulati, M., Hartmark-Hill, J. R., Mallin, E., Lucio, F., Parrish, J., Muhammad, S., Nelson, L. R., Omalley, C. W., Garcia-Filion, P., Mahnert, N., Federico, G., Titelbaum, A. R., Gonzales, R. J., Herbst-Kralovetz, M., Hale, T., & Gallitano-Mendel, A. L. (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.
- Garvin, A. M., Perez, O., McCormick, B. A., & Hale, T. (2018, April). Impact of Chronic Angiotensin Treatment on the Responses of Isolated Cardiac Fibroblasts to Acute Pro-Fibrotic Stimuli. Experimental Biology.
- Garvin, A. M., Perez, O., McCormick, B. A., & Hale, T. (2018, October). Impact of Chronic Angiotensin Treatment on the Responses of Isolated Cardiac Fibroblasts to Acute Pro-Fibrotic Stimuli. Arizona Physiological Society.
- Khokhar, B., Garvin, A., Perez, O., & Hale, T. (2018, April). Impact of Transient ACE Inhibition on Cardiac Reactive Oxygen Species Enzyme Expression in Response to Nitric Oxide Synthase Inhibition. Experimental Biology.
- Madhavpeddi, L., Hammond, B. D., Hale, T., & Handa, R. J. (2018, March). Impact of Prenatal Dexamethasone on Plasma Cytokines in Neonatal and Adult Rats. ABRC.
- Madhavpeddi, L., Royal, C. R., Hammond, B. D., Handa, R. J., & Hale, T. (2018, April). Role of Angiotensin II in Cardiovascular Stress Responses in Rats Exposed to Glucocorticoids In Utero. Arizona Physiological Society.
- Madhavpeddi, L., Royal, C. R., Hammond, B. D., Handa, R. J., & Hale, T. (2018, April). Role of Angiotensin II in Cardiovascular Stress Responses in Rats Exposed to Glucocorticoids In Utero. Experimental Biology.
- Perez, O., Garvin, A., & Hale, T. (2018, April). Transient ACE-Inhibitor Treatment Produces Persistent Change in Cardiac Fibroblast Physiology. Experimental Biology.
- Siegel, M., McCormick, B., Nayak, T., & Hale, T. (2018, October). Effect of Angiotensin II and Bradykinin Receptor Antagonism on Reactive Oxygen Species Enzyme Expression. Arizona Physiological Society.
- 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.
- Madhavpeddi, L., Hammond, B. D., Royal, C., Handa, R. J., & Hale, T. (2017, October). Role of Angiotensin II in Cardiovascular Stress Responses in Rats Exposed to Glucocorticoids In Utero. Arizona Physiological Soceity.
- McCormick, B. A., Huot-Marchand, J., deBlois, D., & Hale, T. (2017, April). Impact of Bradykinin B1 Receptor Blockade on Angiotensin II-Induced Cardiac and Aortic Remodeling. Experimental Biology. Northern Arizona University.
- McCormick, B. A., Huot-Marchand, J., deBlois, D., & Hale, T. (2017, October). Impact of Bradykinin B1 Receptor Blockade on Angiotensin II-Induced Cardiac and Aortic Remodeling. Arizona Physiological Society. Northern Arizona University.
- Perez, O., & Hale, T. (2017, October). Impact of Prior ACE Inhibition on Cardiac Fibroblast Physiology. Arizona Physiological Society.
- Abidali, H., Biwer, L. A., Siniard, A. L., DeBoth, M., Huentelman, M. J., Broderick, T. L., & Hale, T. (2016, October). Transient ACE Inhibition Produces Persistent Alterations in Cardiac Gene Expression. Arizona Physiological Society.
- 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.
- 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.
- 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.
- Madhavpeddi, L., Gonzales, R. J., & Hale, T. -. (2015, November). Angiotensin II Modulates Sex Steroid Metabolizing Enzyme and Receptor Expression in Cardiac Fibroblasts From Male and Female Rats. Cardiovascular, Renal, and Metabolic Diseases: Physiology and GenderAmerican Physiological Society.
- Madhavpeddi, L., Hale, T. -., & Gonzales, R. J. (2015, November). Angiotensin II Modulates Sex Steroid Metabolizing Enzyme and Receptor Expression in Cardiac Fibroblasts From Male and Female Rats. Arizona Physiological SocietyAmerican Physiological Society.
- McCormick, B. A., Huot-Marchand, J., Carroll, C., Carrier, S., deBlois, D., & Hale, T. -. (2015, April). Angiotensin II-Induced Erectile Dysfunction Prevented By Bradykinin B1 Receptor Antagonism. Experimental BiologyAmerican Physiological Society.More infoAward winning poster
- O'Neill, L. M., Jarrett, C. L., Crawford, M., Carroll, C., Hale, T. -., Dickinson, J. M., Angadi, S. S., Sweazea, K. L., O'Neill, L. M., Huot-Marchand, J., Carroll, C., Carrier, S., deBlois, D., & Hale, T. -. (2015, November). EVALUATION OF THE VASOPROTECTIVE EFFECTS OF HIGH-INTENSITY EXERCISE PRIOR TO ANTRHACYCLINE CHEMOTHERAPY. Arizona Physiological SocietyAmerican Physiological Society.More infoAward winning poster
- Hale, T. M., Biwer, L. A., Ramaiah, P., Shahid, W., & D'Souza, K. M. (2014, April). Cardioprotective effects of prior transient ACE inhibition - role of cardiac fibroblast. Experimental Biology.
- 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., Gonzales, R. J., Hale, T. M., 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., Madhavpeddi, L., Hale, T. M., Hale, T. M., Gonzales, R. J., & Gonzales, R. J. (2014, November). Impact of Angiotensin II on Sex Steroid Receptors in Human Aortic Smooth Muscle Cells. Arizona Chapter American Physiological Society.
- McCormick, B. A., Huot-Marchand, J., Carroll, C. C., Carrier, S., deBlois, D., & Hale, T. M. (2014, November). Bradykinin B1 Receptor Antagonism Prevents Angiotensin II-Induced Erectile Dysfunction. Arizona Physiological Society.
- D'Souza, K. M., Biwer, L. A., Ramaiah, P., Shahid, W., & Hale, T. M. (2013, November). Role Of Cardiac Fibroblast In Cardioprotective Effects Of Prior Transient Ace Inhibition. Arizona Physiological Society. Phoenix: AZPS.
- 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.
- Hale, T. -., & deBlois, D. (2008, Summer). Brief Antihypertensive Treatment May Protect Against Target Organ Damage. International Society of Hypertension.
Others
- Biwer, L. A., Xu, H., Broderick, T. L., & Hale, T. -. (2012, Spring). “Protection against L-NAME induced cardiac dysfunction persists even after cessation of ACE-inhibitor treatment.”. Experimental Biology.
- D'Souza, K. M., Biwer, L. A., & Hale, T. -. (2012, November). “Role of cardiac fibroblasts in mediating early inflammatory responses in hypertensive heart disease”. Arizona Physiological Society.
- 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.More infoSan Diego, CA
- Tu, D., Biwer, L. A., Shahid, W., Lerberer, M., & Hale, T. -. (2012, Spring). “Anti-inflammatory effects of ACE-inhibition persist following withdrawal of treatment.”. Experimental Biology.
- Biwer, L. A., Shahid, W., Lerberer, M., & Hale, T. -. (2011, November). “Anti-Inflammatory Effects of Ace Inhibition Persist Following Withdrawal of Treatment”. D Tu, Arizona Physiological Society.
- Hale, T. -., Georgi, M. B., Biwer, L. A., & Gonzales, R. J. (2011, October). “Angiotensin II Increases Aromatase and Androgen Receptor Expression in Coronary Vascular Smooth Muscle Cells but Not Cardiac Myofibroblasts”. Physiology of Cardiovascular Disease: Gender Disparities.
- Hoang, L. T., Richards, A., Allen, A. N., Biwer, L. A., Hale, T. -., Mitchell, K. D., Huentelman, M. J., & Barnes, C. A. (2011, November). “Cognitive consequences of the gradual induction of hypertension in middle age using Cyp1a1-Ren2 transgenic rats”. Society for Neuroscience.
- Biwer, L. A., Broderick, T. L., & Hale, T. -. (2010, November). “Transient ACE Inhibitor Treatment in SHR Confers Protection Against L-NAME Induced Diastolic Dysfunction”. Arizona Physiological Society.
- Biwer, L. A., Broderick, T. L., & Hale, T. -. (2010, October). “Improved Left Ventricular Function in Nitric Oxide Deficient Spontaneously Hypertensive Rats Previously Treated With an ACE Inhibitor”. Council for High Blood Pressure Research.
- Hale, T. -., Abidali, A., & deBlois, D. (2010, September). “Decrease in L-NAME-Induced Inflammation of Left Ventricle in SHR Previously Treated With Enalapril”. International Society of Hypertension.
- Hale, T. -., Robertson, S., Burns, K. D., & deBlois, D. (2009, Spring). Brief ACE Inhibition Produces Persistent Changes That Protect Heart but Not Kidney From L-NAME Induced Damage. Experimental Biology.
- Hale, T. -., Duguay, D., Doyon, M., & deBlois, D. (2008, Spring). Aging-Related Changes Reduce the Susceptibility to Antihypertensive Drug-Induced Remodeling in the Aorta of Spontaneously Hypertensive Rats”. International Society of Hypertension.