Shetal H. Padia
Shetal H. Padia, MD
- Associate Professor of Medicine
- Division of Endocrinology and Metabolism
- Department of Medicine
- MD: East Carolina University
- Residency: Internal Medicine, University of Virginia
- Chief Residency: Internal Medicine, University of Virginia
- Fellowship: Endocrinology, University of Virginia
Hypertension is a chronic condition affecting approximately 1/3 of the current U.S. population and is a major risk factor for cardiovascular disease. The vast majority of hypertensive patients have essential or unexplained hypertension and less than half of these patients achieve their blood pressure targets. Obesity-induced hypertension is a primary mediator of vascular mortality and excess weight accounts for up to 2/3 of the risk of essential hypertension. A major proposed mechanism of the increase in blood pressure in response to high fat diet involves a primary increase in renal tubular sodium reabsorption. Normal sodium excretion is then only achieved at the expense of elevated renal perfusion pressure. Over time the kidneys reset to require an elevated blood pressure in order to continue to excrete a normal sodium load (pressure-natriuresis). Insights into pathophysiological mechanisms that are common to different forms of hypertension would facilitate the development of new treatments for this condition.
My laboratory is interested in a novel, intrarenal sodium-retaining system, the ghrelin-ghrelin receptor system. Ghrelin, a 28-amino acid peptide hormone, was originally discovered as a centrally acting orexigenic hormone, but has recently been shown to possess both cardiovascular and sodium retaining properties. We have demonstrated that ghrelin receptors are localized to the collecting duct in the kidney where ghrelin is coupled to an adenylyl cyclase second messenger system to increase renal interstitial cAMP levels and induce ENaC-dependent sodium reabsorption in rats. We have also shown that pharmacological intrarenal ghrelin receptor blockade prevents the development of high fat diet-induced hypertension by preventing the reduction in urine sodium excretion associated with increased ENaC protein expression. Collectively, these studies suggest a role for renal ghrelin receptors in the regulation of sodium flux, thereby adding another layer of complexity to our previous understanding of sodium regulation in the kidney.
Our research is supported by:
- NIH RO1 DK110369-01 (PI Padia, “Intrarenal Mechanisms of Ghrelin in Obesity-Hypertension,” 05/2016-5/2021)
Shetal H. Padia, M.D.
Associate Professor of Medicine
University of Virginia School of Medicine
PO Box 801414, University of Virginia Health System
Charlottesville, VA 22908