Christopher T Banek
- Assistant Professor, Physiology
- Member of the Graduate Faculty
- (520) 621-6068
- Arizona Health Sciences Center, Rm. 425
- Tucson, AZ 85724
- cbanek@arizona.edu
Biography
My laboratory focus is dedicated to investigating the role of peripheral neural control of cardiovascular and kidney health and disease. Our current research projects are focused on studying the role of peripheral sensory nerves in the development and maintenance of (a) hypertension (i.e. high blood pressure) and (b) polycystic kidney disease. Sensory nerves in the kidney appear to also contribute to both the development and maintenance of several models of experimental cardiovascular and kidney disease through a gradual, pathological elevation in renal afferent nerve activity. It is unclear what is driving this change in activity, as well as the physiological responses to both acute and chronic sensory nerve activation. We employ chronic telemetry-based approaches as well as acute electrophysiological preparations to evaluate the changes in nerve activity and the corresponding cardiovascular and renal responses. Additionally, we take a molecular approach to study the particular proteins and non-peptide signals that may be the primary drivers of sensory nerve activation.
https://physiology.arizona.edu/lab-page/banek-lab
https://www.ncbi.nlm.nih.gov/pubmed/?term=banek%20ct
Degrees
- Ph.D. Human Physiology
- University of Oregon, Eugene, Oregon, United States
- Novel Modalities for Preeclampsia Prevention: A Role for Exercise Training and AICAR Administration
- B.A. Chemistry
- University of Minnesota - Duluth, Duluth, Minnesota, United States
- B.S. Biochemistry and Molecular Biology
- University of Minnesota - Duluth, Duluth, Minnesota, United States
Work Experience
- University of Arizona, Tucson, Arizona (2019 - Ongoing)
- University of Minnesota, Minneapolis, Minnesota (2018 - 2019)
- University of Minnesota, Minneapolis, Minnesota (2014 - 2018)
- University of Oregon, Eugene, Oregon (2011 - 2014)
- University of Minnesota - Duluth (2009 - 2011)
Awards
- New Investigator of the Year Award
- American Physiological Society (NCAR Section), Spring 2020
Interests
Research
Hypertension; Salt-sensitive Hypertension; Renal denervation; Autonomic Nervous System; Sensory Nerves; Polycystic Kidney Disease; Chronic Kidney Disease; Preeclampsia; Pregnancy; Vascular Function
Teaching
Cardiovascular physiology; Neurophysiology; Renal physiology
Courses
2023-24 Courses
-
Directed Research
PSIO 492 (Spring 2024) -
Honors Independent Study
PSIO 399H (Spring 2024) -
Honors Independent Study
PSIO 499H (Spring 2024) -
Human Anat+Physiology II
PSIO 202 (Spring 2024) -
Independent Study
PSIO 499 (Spring 2024) -
Directed Research
PSIO 492 (Fall 2023) -
Dissertation
PS 920 (Fall 2023) -
Honors Independent Study
PSIO 499H (Fall 2023) -
Independent Study
PSIO 399 (Fall 2023) -
Rsrch Meth Psio Sci
PS 700 (Fall 2023)
2022-23 Courses
-
Dissertation
PS 920 (Spring 2023) -
Honors Independent Study
PSIO 499H (Spring 2023) -
Honors Thesis
NSCS 498H (Spring 2023) -
Honors Thesis
PSIO 498H (Spring 2023) -
Human Anat+Physiology II
PSIO 202 (Spring 2023) -
Research
PS 900 (Spring 2023) -
Rsrch Meth Biomed Engr
BME 592 (Spring 2023) -
Directed Research
PSIO 492 (Fall 2022) -
Dissertation
PS 920 (Fall 2022) -
Honors Thesis
NSCS 498H (Fall 2022) -
Honors Thesis
PSIO 498H (Fall 2022) -
Research
PS 900 (Fall 2022)
2021-22 Courses
-
Directed Research
PSIO 492 (Spring 2022) -
Dissertation
PS 920 (Spring 2022) -
Honors Independent Study
PSIO 499H (Spring 2022) -
Honors Thesis
PSIO 498H (Spring 2022) -
Research
PS 900 (Spring 2022) -
Thesis
PS 910 (Spring 2022) -
Honors Independent Study
PSIO 399H (Fall 2021) -
Honors Independent Study
PSIO 499H (Fall 2021) -
Honors Thesis
PSIO 498H (Fall 2021) -
Research
PS 900 (Fall 2021) -
Rsrch Meth Psio Sci
PS 700 (Fall 2021) -
Thesis
PS 910 (Fall 2021)
2020-21 Courses
-
Research
PS 900 (Summer I 2021) -
Rsrch Meth Psio Sci
PS 700 (Summer I 2021) -
Directed Research
PSIO 492 (Spring 2021) -
Honors Independent Study
PSIO 399H (Spring 2021) -
Honors Independent Study
PSIO 499H (Spring 2021) -
Honors Thesis
PSIO 498H (Spring 2021) -
Research
PS 900 (Spring 2021) -
Research Methods In Psio
PSIO 610 (Spring 2021) -
Rsrch Meth Psio Sci
PS 700 (Spring 2021) -
Directed Research
PSIO 492 (Fall 2020) -
Honors Independent Study
PSIO 399H (Fall 2020) -
Honors Thesis
PSIO 498H (Fall 2020) -
Rsrch Meth Psio Sci
PS 700 (Fall 2020)
2019-20 Courses
-
Directed Research
PSIO 492 (Spring 2020)
Scholarly Contributions
Chapters
- Gilbert, J. S., & T., C. (2012). Sex Differences in the Developmental Programming of Adult Disease. In Sex Differences in the Developmental Programming of Adult Disease(pp Ch. 15). IntechOpen.
Journals/Publications
- Banek, C. T., Gauthier, M. M., & AlMarabeh, S. (2023). A song of AAs and fire: divergent sex-dependent renal inflammatory mechanisms in hypertensive SLE mice. American Journal of Physiology-Heart and Circulatory Physiology, 324(1), H82-H84. doi:10.1152/ajpheart.00679.2022
- Banek, C. T., Dennis, M. R., Gauthier, M. M., Parvin, I., & Leung, C. H. (2022). Abstract 053: Increased Arterial Pressure Precedes Renal Dysfunction And Elevated Renal Sympathetic And Afferent Nerve Activity In Deoxycorticosterone-Salt Rat. Hypertension, 79(Suppl_1). doi:10.1161/hyp.79.suppl_1.053
- Banek, C. T., Morales, M. N., Dennis, M. R., Gauthier, M. M., & Brooks, H. L. (2022). Contributions of afferent and sympathetic renal nerves to cystogenesis and arterial pressure regulation in a preclinical model of autosomal recessive polycystic kidney disease. American Journal of Physiology-Renal Physiology, 322(6), F680-F691. doi:10.1152/ajprenal.00009.2022
- Banek, C. T., Osborn, J. W., Menani, J. V., Evans, L. C., Collister, J. P., Helden, D. V., Vulchanova, L., Pestana-Oliveira, N., & Lauar, M. R. (2022). Abstract 075: The Kidney-OVLT Neuroaxis Mediates Neurogenic Hypertension And Polydipsia In 2-Kidney, 1-Clip Rats. Hypertension, 79(Suppl_1). doi:10.1161/hyp.79.suppl_1.075More infoRenal afferent nerves mediate activation of the sympathetic nervous system and hypertension in rats with unilateral renal artery stenosis (2K1C-HTN). However, the central neural structures that mediate this response are unclear. The organum vasculosum of the lamina terminalis (OVLT), has also been implicated in the regulation of mean arterial pressure (MAP) and sympathetic activity in preclinical models of hypertension. We tested the hypothesis that afferent renal nerves and the OVLT share a common neural pathway required for the development of 2K1C-HTN. Two experiments were conducted. 1: Male rats (n=5-9) were implanted with telemeters to measure MAP. 1-week later they received a clip on the left renal artery and were subjected to afferent renal denervation (ARDN) by periaxonal capsaicin (2K1C-ARDN) or sham (2K1C-sham) treatment of the clipped kidney. 2: Male rats (n=6-8) were subjected to lesioning of the OVLT (OVLTx) or sham operation. 1-week later telemeters were implanted and 7 days later the left renal artery was stenosed by application of a silver clip. In both experiments, MAP was measured continuously for 6 weeks, and water intake (WI) was measured once a week. Neurogenic pressor activity (NPA) was assessed by measuring the peak MAP response to ganglionic blockade. EXPT 1 Results: At the end of the protocol, MAP was 165±5 mmHg in 2K1C-sham compared to 131±10mmHg in 2K-1C-ARDN rats (p
- Asirvatham-Jeyaraj, N., Gauthier, M. M., Banek, C. T., Ramesh, A., Garver, H., Fink, G. D., & Osborn, J. W. (2021). Renal Denervation and Celiac Ganglionectomy Decrease Mean Arterial Pressure Similarly in Genetically Hypertensive Schlager (BPH/2J) Mice. Hypertension (Dallas, Tex. : 1979), 77(2), 519-528.More infoRenal denervation (RDNX) lowers mean arterial pressure (MAP) in patients with resistant hypertension. Less well studied is the effect of celiac ganglionectomy (CGX), a procedure which involves the removal of the nerves innervating the splanchnic vascular bed. We hypothesized that RDNX and CGX would both lower MAP in genetically hypertensive Schlager (BPH/2J) mice through a reduction in sympathetic tone. Telemeters were implanted into the femoral artery in mice to monitor MAP before and after RDNX (n=5), CGX (n=6), or SHAM (n=6). MAP, systolic blood pressure, diastolic blood pressure, and heart rate were recorded for 14 days postoperatively. The MAP response to hexamethonium (10 mg/kg, IP) was measured on control day 3 and postoperative day 10 as a measure of global neurogenic pressor activity. The efficacy of denervation was assessed by measurement of tissue norepinephrine. Control MAP was similar among the 3 groups before surgical treatments (≈130 mm Hg). On postoperative day 14, MAP was significantly lower in RDNX (-11±2 mm Hg) and CGX (-11±1 mm Hg) groups compared with their predenervation values. This was not the case in SHAM mice (-5±3 mm Hg). The depressor response to hexamethonium in the RDNX group was significantly smaller on postoperative day 10 (-10±5 mm Hg) compared with baseline control (-25±10 mm Hg). This was not the case in mice in the SHAM (day 10; -28±5 mm Hg) or CGX (day 10; -34±7 mm Hg) group. In conclusion, both renal and splanchnic nerves contribute to hypertension in BPH/2J mice, but likely through different mechanisms.
- Banek, C. T., Bradshaw, J. L., Coats, L. E., Alexander, B. T., & Goulopoulou, S. (2021). Getting it right: preventing drift in baseline cardiovascular phenotype when using Sprague-Dawley rats. American journal of physiology. Heart and circulatory physiology, 321(3), H475-H478.
- Banek, C. T., Gauthier, M. M., Asirvatham-Jeyaraj, N., Ramesh, A., Garver, H., Fink, G. D., & Osborn, J. W. (2021). Renal Denervation and Celiac Ganglionectomy Decrease Mean Arterial Pressure Similarly in Genetically Hypertensive Schlager (BPH/2J) Mice. Hypertension, 77(2), 519-528. doi:10.1161/hypertensionaha.119.14069
- Geisler, C. E., Ghimire, S., Hepler, C., Miller, K. E., Bruggink, S. M., Kentch, K. P., Higgins, M. R., Banek, C. T., Yoshino, J., Klein, S., & Renquist, B. J. (2021). Hepatocyte membrane potential regulates serum insulin and insulin sensitivity by altering hepatic GABA release. Cell reports, 35(13), 109298.More infoHepatic lipid accumulation in obesity correlates with the severity of hyperinsulinemia and systemic insulin resistance. Obesity-induced hepatocellular lipid accumulation results in hepatocyte depolarization. We have established that hepatocyte depolarization depresses hepatic afferent vagal nerve firing, increases GABA release from liver slices, and causes hyperinsulinemia. Preventing hepatic GABA release or eliminating the ability of the liver to communicate to the hepatic vagal nerve ameliorates the hyperinsulinemia and insulin resistance associated with diet-induced obesity. In people with obesity, hepatic expression of GABA transporters is associated with glucose infusion and disposal rates during a hyperinsulinemic euglycemic clamp. Single-nucleotide polymorphisms in hepatic GABA re-uptake transporters are associated with an increased incidence of type 2 diabetes mellitus. Herein, we identify GABA as a neuro-hepatokine that is dysregulated in obesity and whose release can be manipulated to mute or exacerbate the glucoregulatory dysfunction common to obesity.
- Banek, C., & Osborn, J. (2020). Renal Afferent Nerve Activation and Arterial Pressure Control: Role of Inflammatory Cytokines in Hypertension. The FASEB Journal, 34(S1), 1-1. doi:10.1096/fasebj.2020.34.s1.05980
- Banek, C. T., Gauthier, M. M., Van Helden, D. A., Fink, G. D., & Osborn, J. W. (2019). Renal Inflammation in DOCA-Salt Hypertension. Hypertension (Dallas, Tex. : 1979), 73(5), 1079-1086.More infoRecent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, because RDN decreases renal perfusion pressure, it is unclear whether these effects are because of the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the deoxycorticosterone (DOCA)-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical RDN or sham (Sham) were administered DOCA (100 mg, SC) and 0.9% saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion was measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt-induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC (growth-related oncogene/keratinocyte chemoattractant), MCP (monocyte chemoattractant protein)-1, and macrophage infiltration were lower in the denervated kidney versus the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cell-specificity mediating these effects require further investigation.
- Kiuchi, M. G., Esler, M. D., Fink, G. D., Osborn, J. W., Banek, C. T., Böhm, M., Denton, K. M., DiBona, G. F., Everett, T. H., Grassi, G., Katholi, R. E., Knuepfer, M. M., Kopp, U. C., Lefer, D. J., Lohmeier, T. E., May, C. N., Mahfoud, F., Paton, J. F., Schmieder, R. E., , Pellegrino, P. R., et al. (2019). Renal Denervation Update From the International Sympathetic Nervous System Summit: JACC State-of-the-Art Review. Journal of the American College of Cardiology, 73(23), 3006-3017.More infoThree recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.
- Banek, C. T., Gauthier, M. M., Baumann, D. C., Van Helden, D., Asirvatham-Jeyaraj, N., Panoskaltsis-Mortari, A., Fink, G. D., & Osborn, J. W. (2018). Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat. American journal of physiology. Regulatory, integrative and comparative physiology, 314(6), R883-R891.More infoRecent preclinical studies show renal denervation (RDNx) may be an effective treatment for hypertension; however, the mechanism remains unknown. We have recently reported total RDNx (TRDNx) and afferent-selective RDNx (ARDNx) similarly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Whereas TRDNx abolished renal inflammation, ARDNx had a minimal effect despite an identical antihypertensive effect. Although this study established that ARDNx attenuates the development of DOCA-salt hypertension, it is unknown whether this mechanism remains operative once hypertension is established. The current study tested the hypothesis that TRDNx and ARDNx would similarly decrease mean arterial pressure (MAP) in the DOCA-salt hypertensive rat, and only TRDNx would mitigate renal inflammation. After 21 days of DOCA-salt treatment, male Sprague-Dawley rats underwent TRDNx ( n = 16), ARDNx ( n = 16), or Sham ( n = 14) treatment and were monitored for 14 days. Compared with baseline, TRDNx and ARDNx decreased MAP similarly (TRDNx -14 ± 4 and ARDNx -15 ± 6 mmHg). After analysis of diurnal rhythm, rhythm-adjusted mean and amplitude of night/day cycle were also reduced in TRDNx and ARDNx groups compared with Sham. Notably, no change in renal inflammation, injury, or function was detected with either treatment. We conclude from these findings that: 1) RDNx mitigates established DOCA-salt hypertension; 2) the MAP responses to RDNx are primarily mediated by ablation of afferent renal nerves; and 3) renal nerves do not contribute to the maintenance of renal inflammation in DOCA-salt hypertension.
- Collister, J. P., Nahey, D. B., Hartson, R., Wiedmeyer, C. E., Banek, C. T., & Osborn, J. W. (2018). Lesion of the OVLT markedly attenuates chronic DOCA-salt hypertension in rats. American journal of physiology. Regulatory, integrative and comparative physiology, 315(3), R568-R575.More infoLesions of the anteroventral third ventricle (AV3V region) are known to prevent many forms of experimental hypertension, including mineralocorticoid [deoxycorticosterone acetate (DOCA)-salt] hypertension in the rat. However, AV3V lesions include the organum vasculosum of the lamina terminalis (OVLT), portions of the median preoptic nucleus, and efferent fibers from the subfornical organ (SFO), thereby limiting the ability to define the individual contribution of these structures to the prevention of experimental hypertension. Having previously reported that the SFO does not play a significant role in the development of DOCA-salt hypertension, the present study was designed to test the hypothesis that the OVLT is necessary for DOCA-salt hypertension in the rat. In uninephrectomized OVLT-lesioned (OVLTx; n = 6) and sham-operated ( n = 4) Sprague-Dawley rats consuming a 0.1% NaCl diet and 0.9% NaCl drinking solution, 24-h mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg sc per rat). No differences in control MAP were observed between groups. The chronic pressor response to DOCA was attenuated in OVLTx rats such that MAP increased to 133 ± 3 mmHg in sham-operated rats by day 21 of DOCA compared with 120 ± 4 mmHg (means ± SE) in OVLTx rats. These results support the hypothesis that the OVLT is an important brain site of action for the pathogenesis of DOCA-salt hypertension in the rat.
- Osborn, J. W., & Banek, C. T. (2018). Catheter-Based Renal Nerve Ablation as a Novel Hypertension Therapy: Lost, and Then Found, in Translation. Hypertension (Dallas, Tex. : 1979), 71(3), 383-388.
- Asirvatham-Jeyaraj, N., Fiege, J. K., Han, R., Foss, J., Banek, C. T., Burbach, B. J., Razzoli, M., Bartolomucci, A., Shimizu, Y., Panoskaltsis-Mortari, A., & Osborn, J. W. (2016). Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice. Hypertension (Dallas, Tex. : 1979), 68(4), 929-36.More infoHypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.
- Banek, C. T., Knuepfer, M. M., Foss, J. D., Fiege, J. K., Asirvatham-Jeyaraj, N., Van Helden, D., Shimizu, Y., & Osborn, J. W. (2016). Resting Afferent Renal Nerve Discharge and Renal Inflammation: Elucidating the Role of Afferent and Efferent Renal Nerves in Deoxycorticosterone Acetate Salt Hypertension. Hypertension (Dallas, Tex. : 1979), 68(6), 1415-1423.More infoRenal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA) salt rat model. Uninephrectomized male Sprague-Dawley rats (275-300 g) underwent afferent-selective RDNx (n=10), total RDNx (n=10), or Sham (n=10) and were instrumented for the measurement of mean arterial pressure and heart rate by radiotelemetry. Rats received 100-mg DOCA (SC) and 0.9% saline for 21 days. Resting afferent renal nerve activity in DOCA and vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting afferent renal nerve activity, expressed as a percent of peak afferent nerve activity, was substantially increased in DOCA than in vehicle (35.8±4.4 versus 15.3±2.8 %Amax). The DOCA-Sham hypertension (132±12 mm Hg) was attenuated by ≈50% in both total RDNx (111±8 mm Hg) and afferent-selective RDNx (117±5 mm Hg) groups. Renal inflammation induced by DOCA salt was attenuated by total RDNx and unaffected by afferent-selective RDNx. These data suggest that afferent renal nerve activity may mediate the hypertensive response to DOCA salt, but inflammation may be mediated primarily by efferent renal sympathetic nerve activity. Also, resting afferent renal nerve activity is elevated in DOCA salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.
- Banek, C. T., Bauer, A. J., Needham, K. M., Dreyer, H. C., & Gilbert, J. S. (2013). AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat. American journal of physiology. Heart and circulatory physiology, 304(8), H1159-65.More infoPrevious studies suggest restoration of angiogenic balance can lower blood pressure and improve vascular endothelium function in models of preeclampsia. Our laboratory has recently reported exercise training mitigates hypertension in an animal model of preeclampsia, but the mechanisms are unknown. AMP-activated protein kinase (AMPK) is stimulated during exercise and has been shown to increase expression of VEGF. Therefore, the purpose of this study was to determine whether AICAR (5-aminoimidazole-4-carboxamide-3-ribonucleoside), a potent AMPK stimulator, would increase circulating VEGF, improve angiogenic potential, decrease oxidative stress, and abrogate placental ischemia-induced hypertension. In rats, reduced uteroplacental perfusion pressure (RUPP) was induced on day 14 of gestation by introducing silver clips on the inferior abdominal aorta and ovarian arteries. AICAR was administered intraperitoneally (50 mg/kg b.i.d.) days 14-18, and blood pressure and tissues were collected on day 19. RUPP-induced hypertension was ameliorated (P < 0.05) with AICAR versus RUPP. AICAR increased (P < 0.05) plasma VEGF and decreased (P < 0.05) plasma soluble VEGF receptor-1 in the RUPP + AICAR versus RUPP. Antioxidant capacity was restored (P < 0.05) by AICAR in RUPP placenta. Renal and placental catalase activity was decreased (P < 0.05) in RUPP + AICAR versus RUPP. Angiogenic potential was increased (P < 0.05) in RUPP + AICAR versus RUPP. Fetal and placental weights were unaffected by AICAR. Placental AMPK phosphorylation was increased (P < 0.05) in RUPP + AICAR versus normal pregnant and RUPP. These findings suggest AICAR may be useful to mitigate angiogenic imbalance, renal, and placental oxidative stress and increase in blood pressure associated with RUPP hypertension. Furthermore, placental AMPK phosphorylation was observed only in the setting of ischemia.
- Bauer, A. J., Banek, C. T., Needham, K., Gillham, H., Capoccia, S., Regal, J. F., & Gilbert, J. S. (2013). Pravastatin attenuates hypertension, oxidative stress, and angiogenic imbalance in rat model of placental ischemia-induced hypertension. Hypertension (Dallas, Tex. : 1979), 61(5), 1103-10.More infoPreeclampsia is a pregnancy-specific condition characterized by an imbalance of circulating angiogenic factors and new-onset hypertension. Although current treatment options are limited, recent studies suggest that pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin would restore angiogenic balance and reduce mean arterial pressure (MAP) in rats with reduced utero-placental perfusion pressure (RUPP)-induced hypertension. Pravastatin was administered intraperitoneally (1 mg/kg per day) in RUPP (RUPP+P) and normal pregnant rats (NP+P) from day 14 to 19 of pregnancy. On day 19, MAP was measured via catheter, conceptus data were recorded, and tissues collected. MAP was increased (P
- Gilbert, J. S., Banek, C. T., Babcock, S. A., & Dreyer, H. C. (2013). Diabetes in early pregnancy: getting to the heart of the matter. Diabetes, 62(1), 27-8.
- Banek, C. T., Bauer, A. J., Gingery, A., & Gilbert, J. S. (2012). Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat. American journal of physiology. Regulatory, integrative and comparative physiology, 303(6), R658-64.More infoIncreased uterine artery resistance and angiogenic imbalance characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased free vascular endothelial growth factor (VEGF) are often associated with placental insufficiency and preeclampsia but not synonymous with hypertension. We hypothesized chronic reductions in utero-placental perfusion (RUPP) for 5 days (d) during either mid- (d12-d17) or late (d14-d19) gestation would have disparate effects on plasma sFlt-1 and VEGF levels and blood pressure. Five days of chronic RUPP was achieved by placement of silver clips on the abdominal aorta and ovarian arteries on either gestational d12 or d14. Arterial pressure was increased (P < 0.05) in RUPP vs. normal pregnant (NP) in both d17 (10%) and d19 (25%) groups, respectively. Circulating free VEGF was decreased (P < 0.05) and sFlt-1:VEGF ratio increased (P < 0.05) after 5 days of RUPP ending on d19 but not d17 compared with NP controls. Angiogenic imbalance, measured by an endothelial tube formation assay, was present in the d19 RUPP but not the d17 RUPP compared with age-matched NP rats. Five days of RUPP from days 14 to 19 decreased fetal and placental weights 10% (P < 0.01) compared with d19 NP controls. After 5 days of RUPP, from days 12 to 17 of pregnancy, fetal weights were 21% lighter (P < 0.01) compared with d17 NP controls, but placental weight was unchanged. These findings suggest that the timing during which placental insufficiency occurs may play an important role in determining the extent of alterations in angiogenic balance, fetal growth restriction, and the severity of placental ischemia-induced hypertension.
- Gilbert, J. S., Banek, C. T., Bauer, A. J., Gingery, A., & Dreyer, H. C. (2012). Placental and vascular adaptations to exercise training before and during pregnancy in the rat. American journal of physiology. Regulatory, integrative and comparative physiology, 303(5), R520-6.More infoAlthough exercise during pregnancy is generally recommended and thought to be beneficial to mother and fetus, the nature of the adaptations to exercise during pregnancy and how they may be beneficial remain poorly understood. Recent studies suggest that exercise may stimulate expression of several cytoprotective and pro-angiogenic molecules such as heat shock proteins (HSP) and vascular endothelial growth factors (VEGF). We hypothesized that exercise training during pregnancy improves angiogenic balance, increases HSP expression, and improves endothelial function. Female rats were given access to an exercise wheel for 6 wk before and during pregnancy. On day 19 of pregnancy tissues were collected and snap frozen for later analysis. Western blots were performed in skeletal muscle and placenta. HSP 27 (3.7 ± 0.36 vs. 2.2 ± 0.38; P < 0.05), HSP 60 (2.2 ± 0.73 vs. 0.49 ± 0.08; P < 0.05), and HSP 90 (0.33 ± 0.09 vs. 0.11 ± 0.02; P < 0.05) were increased in the placentas of exercise-trained rats compared with sedentary controls. In addition, exercise training increased (P < 0.05) plasma free VEGF and augmented (P < 0.05) endothelium-dependent vascular relaxation compared with nonexercise control rats. The present data indicates chronic exercise training stimulates HSP expression in the placenta and that regular exercise training increases circulating VEGF in pregnant but not in nonpregnant rats. Although the present findings suggest that exercise before and during pregnancy may promote the expression of molecules that could attenuate placental and vascular dysfunction in complicated pregnancies, further studies are needed to determine the safety and effectiveness of exercise training as a therapeutic modality in pregnancy.
- Gilbert, J. S., Banek, C. T., Bauer, A. J., Gingery, A., & Needham, K. (2012). Exercise training attenuates placental ischemia-induced hypertension and angiogenic imbalance in the rat. Hypertension (Dallas, Tex. : 1979), 60(6), 1545-51.More infoAn imbalance between proangiogenic (vascular endothelial growth factor) and antiangiogenic (soluble fms-like tyrosine kinase 1) factors plays an important role in hypertension associated with reduced uteroplacental perfusion (RUPP). Exercise has been shown to stimulate proangiogenic factors, such as vascular endothelial growth factor, in both the pregnant and nonpregnant state; thus, we hypothesized that exercise training would attenuate both angiogenic imbalance and hypertension attributed to RUPP. Four groups of animals were studied, RUPP and normal pregnant controls and normal pregnant and RUPP+exercise training. Exercise training attenuated RUPP-induced hypertension (P
- Gilbert, J. S., Banek, C. T., Katz, V. L., Babcock, S. A., & Regal, J. F. (2012). Complement activation in pregnancy: too much of a good thing?. Hypertension (Dallas, Tex. : 1979), 60(5), 1114-6.
- Gilbert, J. S., Bauer, A. J., Gilbert, S. A., & Banek, C. T. (2012). The opposing roles of anti-angiogenic factors in cancer and preeclampsia. Frontiers in bioscience (Elite edition), 4, 2652-69.More infoHypertensive disorders of pregnancy such as preeclampsia present an increasing source of concern during gestation and accumulating evidence suggests there are long-term effects on the subsequent health of the mother and child. While formerly preeclamptic women have increased risk for later cardiovascular disease, they appear to have decreased risk of some cancers. Recent investigations have revealed exciting insights into potential mechanisms underlying the pathogenesis of preeclampsia and some of these findings may bear relevance to the attenuated cancer risk reported in the literature. Placental ischemia, regarded as a primary initiating factor in preeclampsia, results in elevated levels of factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin/CD105 (sEng) that generate profound effects on the vascular endothelium and cardiovascular function. Further, these factors may also influence development of susceptible organs such as the mammary. Moreover, recent evidence suggests these molecules may be regulated by factors derived from cigarette smoke. Taken together, elucidating mechanisms linking placental ischemia, endothelial function and subsequent cancer risk is an important step towards identifying novel therapies for cancer.
- Gilbert, J. S., Bauer, A. J., Gingery, A., Banek, C. T., & Chasson, S. (2012). Circulating and utero-placental adaptations to chronic placental ischemia in the rat. Placenta, 33(2), 100-5.More infoWhile utero-placental insufficiency is associated with adverse outcomes for both mother and fetus, many of the maternal-fetal adaptations during pregnancy in models of fetal compromise remain unclear. The purpose of this study was to determine if chronically reduced uterine perfusion pressure (RUPP) during days 14-19 of gestation alters feto-placental growth differentially from the cervical to ovarian ends of the uterus and generates metabolic adaptations such as increased blood lactate (BLa) concentrations and lactate transporter expression in the placenta. Fetal growth restriction was evident, placental efficiency (fetal weight/placental weight) decreased (4.7 ± 0.35 vs. 5.9 ± 0.30; P
- Banek, C. T., & Gilbert, J. S. (2011). Approaching the threshold for predicting preeclampsia: monitoring angiogenic balance during pregnancy. Hypertension (Dallas, Tex. : 1979), 58(5), 774-5.
- Yoshimura, A., Banek, C. T., Yusubov, M. S., Nemykin, V. N., & Zhdankin, V. V. (2011). Preparation, X-ray structure, and reactivity of 2-iodylpyridines: recyclable hypervalent iodine(V) reagents. The Journal of organic chemistry, 76(10), 3812-9.More info2-Iodylpyridine and four examples of 3-alkoxy-2-iodylpyridines were prepared by oxidation of the respective 2-iodopyridines with 3,3-dimethyldioxirane. Structures of 2-iodylpyridine, 2-iodyl-3-isopropoxypyridine, and 2-iodyl-3-propoxypyridine were established by single-crystal X-ray diffraction analysis. 2-Iodyl-3-propoxypyridine has moderate solubility in organic solvents (e.g., 1.1 mg/mL in acetonitrile) and can be used as a recyclable reagent for oxidation of sulfides and alcohols. The reduced form of this reagent, 2-iodo-3-propoxypyridine, can be effectively separated from the reaction mixture by treatment with diluted sulfuric acid and recovered from the acidic aqueous solution by adding aqueous sodium hydroxide.
- Zagulyaeva, A. A., Banek, C. T., Yusubov, M. S., & Zhdankin, V. V. (2010). Hofmann rearrangement of carboxamides mediated by hypervalent iodine species generated in situ from iodobenzene and oxone: reaction scope and limitations. Organic letters, 12(20), 4644-7.More infoAlkylcarboxamides can be converted to the respective amines by Hofmann rearrangement using hypervalent iodine species generated in situ from PhI and Oxone in aqueous acetonitrile. On the basis of this reaction, a convenient experimental procedure for the preparation of alkylcarbamates using Oxone as the oxidant in the presence of iodobenzene in methanol has been developed. An efficient method for direct conversion of substituted benzamides to the respective quinone derivatives by treatment with Oxone and iodobenzene in aqueous acetonitrile has also been found.