The principal objective of our research program is to elucidate the biochemical, physiological, and pathophysiological roles of nitric oxide
(NO) in mammalian cell function. Our studies focus on the transcriptional, translational and regulation of nitric oxide synthases (NOS) as well as the role of other biochemical pathways in the regulation of the biosynthesis and metabolism of nitric oxide. We are utilizing various in vitro and in vivo model systems in a vertically-integrated proposal for our studies. The advantages of a vertically-integrated proposal are that observations from the cellular level can be applied to the intact animal to assess the actual physiological and/or pathophysiological relevance of the proposed mechanisms. In addition, observations from the intact animal can be focused down to changes on the cellular level. Whole animal physiology, cell culture, protein biochemical, molecular biological, and immunohistochemical techniques are all employed in the laboratory.

In collaboration with Dr. David Pollock at MCG, we are studying the relationship between the endothelin (ET) system and the NO pathway in the kidney. We have hypothesized that ET plays an essential role in stimulating renal NO production within the collecting duct in response to increased salt load. These studies have led us to conclude that the ET system and NO pathways are inter-related in the maintenance of sodium reabsorption and sodium excretion in the kidney.

In collaboration with investigators at the Georgia Prevention Institute, we are studying the molecular mechanisms of stress-mediated increases in blood pressure both acutely and chronically. We have discovered that oxidative stress-mediates the acute increase in blood pressure in animals with a genetic background predisposed to hypertension; however animals with no predisposition to hypertension do not have increases in oxidative stress. This mechanism is now being explored in human studies. We have also discovered animals exposed to a stressor early in life have exaggerated stress responses later in life, however animals that are deficient in the ETB receptor do not display this exaggerated response. We have concluded that the ETB receptor signaling pathway is critical in early life stress responses.

We are also actively working on studies investigating the cellular and molecular mechanisms that regulate NOS and NO production in small resistance arteries of the mesenteric and renal circulation. We have found that the regulation of NOS activation in small resistance arteries is very distinct from large conduit arteries. This is very significant because the small resistance arteries regulate vascular tone, organ blood flow, and blood pressure.

Another major focus of the lab is related to the role of NO in the kidney in diabetic nephropathy. These studies are in collaboration with Dr. Pamela Carmines at the University of Nebraska. These studies address the general hypothesis that NADPH oxidase activation and NOS-uncoupling contribute to renal cortical and oxidative stress in diabetes mellitus, with consequent effects on NO bioavailability and action that ultimately diminish its impact on renal function and may lead to kidney failure.

Grant Support as Principal Investigator

2006-2008 PhRMA Foundation Award
Funds to provide travel expenses and honoraria for guest lecturers for the course, Modern Drug Discovery and Development.

1999-2007 NIH R01 (J. Pollock, PI);
Renewed in 2003 Nitric Oxide and Endothelin Interactions in the Kidney

2000-2008 NIH R01(D. Pollock, PI; J. Pollock, co-investigator);
Renewed in 2004 Endothelin Regulation of Kidney Function

2002-2007 NIH Program Project Grant (F. Treiber, Project Director)
Stress Related Mechanisms of Hypertension Risk
Project 4 Vascular and Renal Responses to Stress in Rats (J. Pollock, project leader)
Core B Biochemical and Bioassay Core (J. Pollock, co-core director)

2004-2009 American Heart Association Established Investigator Award (J. Pollock, PI)
Regulation of vascular nitric oxide synthase 1 in normotensive and hypertensive arteries

2004-2008 NIH R01 (E. Inscho, PI; J. Pollock, collaborator)
Purinergic regulation of the renal microvasculature

2004-2009 NIH Program Project Grant (R.C. Webb, Project Director)
Cytokines and Angiotensin-induced Hypertension
Project 4: Endothelin receptor actions and salt-dependent hypertension (J. Pollock, co-investigator)
Core C Biochemistry Core (J. Pollock, core director)

Honors and Awards

Invited Speaker

AHA - Established Investigator Award

Lab

Selected Publications (Within 5 years)

Brophy, C.M., Knoepp, L., Xin, J., and Pollock, J.S. Functional expression of NOS 1 in vascular smooth muscle. Am. J. Physiol., 278: H991-H997, 2000.

Treiber, F.A., Jackson, R.W., Davis, H., Pollock, J.S., Kapuku, G., Mensah, G.A., and Pollock, D.M. Racial differences in endothelin-1 at rest and in response to acute stress in adolescent males. Hypertension, 35: 722-725, 2000.

Cai,Z., Xin, J., Pollock, D.M., and Pollock, J.S. Shear stress-mediated nitric oxide production in inner medullary collecting duct cells. Am. J. Physiol. 279: F270, 2000.

Pollock, D.M., Allcock, G.H., Krishnan, A., Dayton, D.B., and Pollock, J.S. Upregulation of endothelin B receptors in kidneys of DOCA-salt hypertensive rats. Am. J. Physiol., 278: F279-F286, 2000.

Pollock, J.S., Webb, W., Callaway, D., Sathyanarayana, O'Brien, W., and Howdieshell, T.R. Nitric oxide synthase isoform expression in a porcine model of granulation tissue formation. Surgery, 129: 341-350, 2001.

Ishii, N., Patel, K.P., Lane, P., Taylor, T., Bian, K., Murad, F., Pollock, J.S., and Carmines, P.K. Nitric oxide synthesis and degradation in the renal cortex of rats with diabetes mellitus. J. Am. Soc. of Nephrology, 12: 1630-1639, 2001.

Pollock, D.M., Derebail, V.K., Yamamoto, T., and Pollock, J.S. Combined effects of AT1 and ETA receptor antagonists, candesartan and A-127722, in DOCA-salt hypertensive rats. Gen. Pharmacology, 34: 337-342, 2000.

Pollock, D.M. and Pollock, J.S. High salt intake increases the hypertension produced by chronic ETB receptor blockade in Sprague-Dawley rats. Am. J. Physiol., 281: F144-F150, 2001.

Jackson, R.W., Treiber, F.A., Harshfield, G.A., Waller, J.L., Pollock, J.S., and Pollock, D.M. Urinary excretion of vasoactive factors are correlated to sodium excretion. Am. J. Hypertension, 14: 1003-1006, 2001.

Sullivan, J.C., Pollock, D.M., and Pollock, J.S. Altered NOS 3 distribution in mesenteric arteries of hypertensive rats. Hypertension, 39: 597-602, 2002.

Sasser, J.M., J.S. Pollock, and D.M. Pollock. Renal endothelin in chronic angiotensin II hypertension. Am. J. Physiol. Integ. & Comp. Physiol. 283:R243-R248, 2002.

Sullivan, J.C., A.D. Giulumian, D.M.Pollock, L.C. Fuchs, and J.S. Pollock. Functional NOS 1 in rat mesenteric arterial bed. Am. J. Physiol. Heart & Circ. Physiol. 283:H658-H663, 2002.

Treiber, F., G.K. Kapuku, H. Davis, J.S. Pollock, and D.M. Pollock. Plasma endothelin-1 release during acute stress: role of ethnicity and sex. Psychosomatic Medicine 64: 707-713, 2002.

Snieder, H., G.A. Harshfield, P. Barbeau, D.M. Pollock, J.S. Pollock, and F.A. Treiber. Dissecting the genetic architecture of the cardiovascular and renal stress response. Biological Psychology, 61:73-95, 2002.

Taylor, T.A., C. E. Gariepy, D. M. Pollock, J.S. Pollock. Unique endothelin receptor binding in kidneys of ETB receptor deficient rats. Am. J. Physiol. 284: R674-R681, 2003.

Taylor, T.A., C.E. Gariepy, D. M. Pollock, J.S. Pollock. Gender differences in ET and NOS systems in ETB receptor deficient rats: Effect of a high salt diet. Hypertension 41: 657-662, 2003.

Sullivan, J.C. and J. S. Pollock. NOS 3 subcellular localization in the regulation of nitric oxide production. Acta Physiol Scand 179: 115-122, 2003.

Treiber, F.A., P. Barbeau, G. Harshfield, H-S Kang, D. M. Pollock, J. S. Pollock, and H. Snieder. The Endothelin-1 gene lys198asn polymorphism and blood pressure reactivity. Hypertension 42: 494-499, 2003.

Sasser, J.M., J.C. Sullivan, A. Elmarakby, B.E. Kemp, D. M. Pollock, J.S. Pollock. Reduced NOS3 phosphorylation mediates reduced NO/cGMP signaling in mesenteric arteries of DOCA-salt hypertensive rats. Hypertension 43: 1080-1085, 2004.

Sullivan, J.C., E.D. Loomis, M. Collins, J.D. Imig, E.W. Inscho, and J. S. Pollock. Age-related alterations in NOS and oxidative stress in mesenteric arteries from male and female rats. J. Applied Physiology, 97: 1268-1274, 2004.

Malhotra, S., F.A. Treiber, J. Poole, J.S. Pollock, D. Ludwig, and H. Snieder. Interactive effects of NOS3 Glu298Asp polymorphism and obesity upon hemodynamic and nitric oxide reactivity to behavioral stress. Hypertension 44: 866-871, 2004.

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

Elmarakby, A.A., E.D. Loomis, J.S. Pollock, D.M. Pollock. ETA receptor blockade attenuates hypertension and decreases reactive oxygen species in ETB receptor-deficient rats. J. Cardiovas. Pharm. 44: S7-S10, 2004.

Lee, D.L., J.M. Sasser, J. Hobbs, A. Boriskie, D. M. Pollock, P.K. Carmines, and J. S. Pollock. Post-translational regulation of NO synthase activity in the renal medulla of diabetic rats. Am. J. Physiology: Renal 288: F82-F90, 2005.

D'Angelo, G., J.S. Pollock, D.M. Pollock. Endogenous endothelin attenuates the pressor response to acute environmental stress via ETA receptors. Am. J. Physiology: Heart, 288: H1829-35, 2005.

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

Sullivan, J.C., Sasser, J.M., D.M. Pollock, J.S. Pollock. Sexual dimorphism in renal production of prostanoids in spontaneously hypertensive rats. Hypertension, 45: 406-411, 2005.

Pollock, DM and JS Pollock. Endothelin and oxidative stress in the vascular system. Curr Vasc Pharmacol 3: 365-367, 2005.

Pollock, DM and Pollock, JS. Endothelin and oxidative stress in the vascular system. Curr Vasc pharmacol 3: 365-367, 2005.

Loomis, E.D., J.C. Sullivan, D. Osmond, D. M. Pollock, J.S. Pollock. Endothelin mediates superoxide production and vasoconstriction through activation of NADPH oxidase and uncoupled nitric oxide synthase in the rat aorta. J. Pharmacol Exp Ther., 315: 1058-1064, 2005.

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

Sullivan, JC, Pollock, JS, Pollock, DM. Superoxide-Dependent Hypertension in Male and Female ETB Receptor Deficient Rats. Experimental Biology and Medicine, 231: 818-823, 2006.

Pollock, JS and Carmines, PK. Editorial Commentary. NOS3 Regulation: Renal tubular epithelial cells are not simply large endothelial cells. Hypertension 47: 19-21, 2006.

Sullivan, JC and Pollock, JS. Editorial Commentary. Coupled and Uncoupled NOS: Separate But Equal? Uncoupled NOS in endothelial cells is a critical pathway for intracellular signaling. Circulation Research 98: 717-719, 2006.

Sullivan, JC, JM Sasser, JS Pollock. Sexual dimorphism in oxidant status in spontaneously hypertensive rats. Am J Physiol: Regulatory, Integrative, and Comparative Physiology, in press, 2006.

Elmarakby, A., J.M. Williams, J.S. Pollock, D.M. Pollock. Synergistic actions of enalapril and tempol during chronic angiotensin II induced hypertension. Manuscript submitted.

Sasser, J.M., J.C. Sullivan, J.L. Hobbs, T. Yamamoto, D.M. Pollock, P.K. Carmines, J.S. Pollock. Endothelin A receptor blockade reduces diabetic renal injury via an anti-inflammatory mechanism. Manuscript submitted.

Kang, K-T., J.C. Sullivan, J.M. Sasser, J.D. Imig, J.S. Pollock. Novel NOS-dependent mechanism of vasorelaxation in small arteries from hypertensive rats. Manuscript in revision.

Sullivan, J.C., L. Sumpruno-Priete, E. Boesen, D.M. Pollock, J.S. Pollock. Sexual dimorphism in oxidant status in spontaneously hypertensive rats. Manuscript submitted.

Education and Training

Research Experience & Academic Appointments