It seems intuitive that men and women are different, yet this basic fact has been slow to penetrate the scientific community. There is growing awareness, however, that there are differences between the sexes in a number of systems involved in the regulation of blood pressure and chronic kidney disease. My research interests are foucused on identifiying mechanisms that contribute to observed sex differences in cardiovascular disease progression. The approach often taken assumes that the basis of the renal injury is similar in males and females; just the magnitude of the response differs. However, based on the vast number of differences that have been identified in cardiovascular physiology, pathophysiology, and pharmacology it is not unreasonable to propose that the pathway by which males and females develop cardiovascular and renal diseases may be distinct. Two basic systems are currently being investigated in the labaoratory, the nitric oxide-cGMP pathway and the renin-angiotensin system.

Nitric oxide (NO) is important in the control of blood pressure and renal hemodynamics and NO deficiency is linked with the development of hypertension and the progression of chronic renal disease. NO levels have been reported to be greater in females, potentially due to the presence of estrogen. Therefore, a gender difference in the levels of NO may contribute to sex differences in hypertension and renal injury. NO levels are determined by (1) expression/activity of the enzyme NO synthase (NOS) and (2) inactivation of NO by superoxide. Not only have NO levels been suggested to be greater in females, but superoxide levels have been shown to be less. On going studies in the laboratory are examining the molecular mechanisms regulating NOS in the kidney and vasculature and the role of NOS in maintaining blood presure and renal health. Additional studies are probing the role of estrogen in promoting NO.

The RAS is a key system in controlling blood pressure and body fluid volume and over activation of the RAS has been shown to play a critical role in the development and progression of hypertension and renal injury. The RAS is known to be influenced by the sex chromosomal complement of the animal and sex hormones, with plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity and expression, and AT1 receptor expression levels being greater in kidneys from males compared to females. Despite these well acknowledged differences between the sexes in the RAS, inhibitors of the RAS including ACE inhibitors and angiotensin receptor blockers (ARBs) are the most commonly prescribed pharmaceutical treatments for renal disease. While both ACE inhibitors and ARBs have been shown to block the development of renal injury in male experimental animals, the data is not as compelling to support a role for the classical RAS in mediating hypertension and renal disease in females. On going studies in the laboratory are looking at differences in males and females concerning the metabolism of Ang II, differential Ang receptor expression and activation and differential activation of signal transduction cascades.

Grant Support as Principal Investigator

American Heart Association Scientist Development Grant

Honors and Awards

Invited Speaker

Selected Publications

Journal Articles

Case J and Davison CA. Estrogen alters relative contributions of nitric oxide and cyclooxygenase products to endothelium-dependent vasodilation. J Pharm Exp Ther 291:524-530, 1999.

Sullivan JC and Davison CA. Effect of age on electrical field stimulation (EFS)-induced endothelium-dependent vasodilation in male and female rats. Cardiovascular Res 50:137-144, 2001.

Sullivan JC, Pollock DM, and Pollock JS. Altered Nitric Oxide Synthase 3 Distribution in Mesenteric Arteries of Hypertensive Rats. Hypertension, 39:597-602, 2002.

Sullivan JC, Giulumian AD, Pollock DM, Fuchs LC, and Pollock JS. Functional NOS 1 in the Rat Mesenteric Arterial Bed. Am J Physiol, 283:H658-H663, 2002.

Sullivan JC and Pollock JS. NOS 3 Subcellular Localization in the Regulation of Nitric Oxide Production. Acta Phys Scand, 179(2):115-22,2003.

Sullivan JC, Loomis ED, Collins MH, Imig JD, Inscho EW, and Pollock JS. Age-related alterations in NOS and oxidative stress in mesenteric arteries from male and female rats. J Appl Physiol, 97(4):1268-74, 2004.

Sullivan JC, Sasser JM, Pollock, DM, Pollock JS. Sexual dimorphism in renal production of prostanoids in Spontaneously Hypertensive Rats. Hypertension, 45:406-411,2005.

Sullivan JC, Pollock JS, and Pollock DM. Superoxide-dependent hypertension in male and female ETB receptor deficient rats. Exp Biol Med. 231(6):818-823, 2006.

Sullivan JC and Pollock JS. Coupled and Uncoupled NOS: Separate but Equal? Uncoupled NOS in endothelial cells is a critical pathway for intracellular signaling. Circ Res. 98(6):717-719, 2006.

Sullivan JC, Sasser JM, Pollock JS. Sexual Dimorphism in Oxidant Status in Spontaneously Hypertensive Rats. Am J Physiol. 292(2):R764-R768, 2007.

Sullivan JC, Semprun-Prieto L, Boesen EI, David M. Pollock, Pollock JS. Sex and Sex Hormones Influence the Development of Albuminuria and Renal Macrophage Infiltration in Spontaneously Hypertensive Rats. Am J Physiol Regulatory. 293:R1573-R1579, 2007.

Sullivan JC, Goodchild TT, Cai Z, Pollock DM, Pollock JS. ETA and ETB mediated regulation of NOS isoforms in the renal inner medulla. Acta Phys,191:329-336, 2007.

Sullivan JC, Smart EJ, Pollock DM, Pollock JS. Influence of salt on subcellular localization of NOS activity and expression in the renal inner medulla. Clinical Exp Pharmacol Physiol. 35(2):120-125, 2008.

Sullivan JC. Sex and the Renin-Angiotensin System: Ineuqality Between the Sexes in Response to RAS Stimulation and Inihbition. Am J Physiol Regulatory. in press.

Education and Training

Research Experience & Academic Appointments