The overall goal of my laboratory is to elucidate the physiological and pathophysiological role of endothelial-derived factors in the control of renal function relative to hypertension and cardiovascular disease. The work in my laboratory utilizes an integration of animal models with cellular and biochemical approaches. With this multifaceted approach, my laboratory is exploring physiological and pathophysiological mechanisms of vasoactive mediators including endothelin, nitric oxide, and superoxide. These studies involve both hemodynamic and renal tubular mechanisms. Our studies have demonstrated that endothelin normally functions to stimulate nitric oxide production in the renal medulla as a means of facilitating the excretion of salt. We hypothesize that in salt-dependent forms of hypertension, this pathway of salt elimination is interrupted through generation of reactive oxygen species, in particular, superoxide.

We have demonstrated an important role for endothelin ETA receptors in producing elevations in arterial pressure in a variety of genetic and experimental rat and mouse models of salt-dependent hypertension. Furthermore, we have demonstrated that ETB receptors within the kidney operate to oppose these actions such that hypertension depends upon the balance between these two receptor subtypes. Additional studies focus more specifically on a variety of physiological mechanisms by which ETB receptors may control sodium and water excretion and thus contribute to arterial pressure regulation. In a long-standing collaboration with Dr. Jennifer Pollock, we are exploring the role of nitric oxide synthase isoforms in the control of renal excretory function and how they mediate the actions of ETB receptor activation.

We are also working with several other investigators in our effort to determine how different endothelin receptor systems function to control renal hemodynamics and sodium excretion. This includes work with Dr. Edward Inscho in the Department of Physiology to determine endothelin receptor subtype actions within the renal microcirculation. Our hypothesis is that differences in ETA and ETB receptor expression determine unique physiological actions of the endothelin system to control sodium excretion in salt-dependent hypertension. Furthermore, we are working with Dr. David Webb at the University of Edinburgh to distinguish endothelial versus renal tubular ETB receptor actions in the kidney. In collaboration with Dr. Donald Kohan at the University of Utah, we are utilizing collecting-duct specific knockout mice to determine the role of renal medullary endothelin in the control of salt and water balance.

Another major collaboration is with investigators at the Georgia Prevention Institute. These studies have been examining environmental stress as a risk factor for hypertension and cardiovascular disease. Our studies utilize animal models of acute and chronic stress to provide mechanistic insight into the environmental and genetic factors that put people at risk for developing hypertension. This work is supported by a Program Project Grant from the National Institutes of Health.

And finally, as a part of another National Institutes of Health Program Project Grant and in collaboration with Drs. Michael Brands, John Imig, Edward Inscho, and Clinton Webb, we are exploring the role of specific cytokines, IL-1beta, IL-6, TNFalpha, and TGFbeta, in the development of angiotensin II dependent hypertension. Our laboratory runs a telemetry facility to monitor long-term blood pressure in a variety of models that has allowed us to collaborate with many other investigators on campus.

Grant Support as Principal Investigator

RO1 HL64776 NIH/NHLBI
Endothelin Regulation of Kidney Function

Established Investigator Award, American Heart Association
Intrarenal Mechanisms of Endothelin Action

PO1 HL74167, NIH/NHLBI
Cytokines and angiotensin II-induced hypertension: Project 4. Endothelin receptor actions in salt-dependent hypertension

T32 HL076146, NIH/NHLBI
Multidisciplinary pre-doctoral training in integrative cardiovascular biology

Honors and Awards

Lab

Recent Invited Lectures

2005 - Workshop on Angiotensin II Receptor Blockade, Gouvieux-Chantilly, France

2006 - DSI Telemetry Users Group Meeting, Chapel Hill, NC

2006 - 4th International Conference on the Biology of Nitric Oxide, Monterrey, CA

2006 - Avosentan Advisory Board, Speedel Pharma, Luzerne, Switzerland

2007 - Featured Topic Speaker, Experimental Biology 2007

2007 - DSI Telemetry Workshop, Experimental Biology 2007

2007 - 9th Annual Meeting for New Research in Cardiovascular and Kidney Disease, Amelia Island, FL

2007 - APS Conference on "Sex and Gender in Cardiovascular-Renal Physiology and Pathophysiology"

Selected Publications

selected from a list of over 110

Williams, J.M., J.S. Pollock, and D.M. Pollock. Arterial pressure response to the antioxidant, tempol, and ETB receptor blockade in rats on a high salt diet. Hypertension 44:770-775, 2004.

Pollock, D.M., J.M. Jenkins, A.K. Cook, J.D. Imig, E.W. Inscho. L-type calcium channels in the renal microcirculatory response to endothelin. Am J Physiol Renal Physiol. 288:F771-F777, 2005.

Elmarakby, A.A., E.D. Loomis, J.S. Pollock, and D.M. Pollock. NADPH oxidase inhibition attenuates oxidative stress but not hypertension produced by chronic ET-1. Hypertension 45: 283-287, 2005.

D'Angelo, G., J.S. Pollock, and D.M. Pollock. Endogenous endothelin attenuates the pressor response to acute environmental stress. Am. J. Physiol. Heart Circ. Physiol. 288:H1829-H1835, 2005.

Williams, J.M., X. Zhao, M.H. Wang, J.D. Imig, and D.M. Pollock. PPAR-alpha activation reduces salt-dependent hypertension during chronic ETB receptor blockade. Hypertension 46:366-371, 2005.

Inscho, E.W., J.D. Imig, A.K. Cook, and D.M. Pollock. ETA and ETB receptors differentially modulate afferent and efferent arteriolar responses to endothelin. Br. J. Pharmacol. 146:1019-26, 2005.

D'Angelo, G., J.S. Pollock, and D.M. Pollock. In vivo evidence for endothelin-1-mediated attenuation of µ-adrenergic stimulation. Am. J. Physiol. Heart Circ. Physiol., 290: H1251-H1258, 2006.

Sullivan, J.C., J.S. Pollock, and D.M. Pollock. Superoxide-dependent hypertension in male and female ETB receptor deficient rats. Exptl. Biol. Med. 231: 818-823, 2006.

Sasser, J.M., J.S. Sullivan, J.L. Hobbs, T. Yamamoto, D.M. Pollock, P.K. Carmines, and J.S. Pollock. Endothelin A receptor blockade reduces diabetic renal injury via an anti-inflammatory mechanisms, but not via reduced oxidative stress. J. Am. Soc. Nephrol. 18: 143-154, 2007.

Boesen, E.I., and D.M. Pollock. Acute increases of renal medullary osmolality stimulate endothelin release from the kidney. Am. J. Physiol. Renal Physiol. 292: F185-F191, 2007.

Schneider, M.P., E.W. Inscho, and D.M. Pollock. Attenuated vasoconstrictor responses to endothelin in afferent arterioles during a high salt diet. Am. J. Physiol. Renal Physiol. 292: F1208-F1214, 2007.

Schneider, M.P., E.I. Boesen, and D.M. Pollock. Contrasting actions of endothelin ETA and ETB receptors in cardiovascular disease. Ann. Rev. Pharmacol. 47: 731-759, 2007.

Education and Training

Research Experience & Academic Appointments

Society Memberships