Access Type

Open Access Dissertation

Date of Award

January 2015

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Physiology

First Advisor

William H. Beierwaltes

Abstract

We investigated the acute and chronic effects of resveratrol on renal function and blood pressure. We hypothesized that resveratrol would act as a renal vasodilator through a nitric oxide-dependent mechanism. In our acute studies, we found an intravenous bolus of resveratrol influenced changes in renal hemodynamics by increasing renal blood flow and decreasing renal vascular resistance. The mechanism of renal vasodilation was nitric oxide dependent and through a reduction of endogenous reactive oxygen species. Resveratrol-induced renal vasodilation was not influenced by COX metabolism and vasodilatory prostanoids. We found with continuous intravenous resveratrol infusion induced significant renal vasodilation while not altering either glomerular filtration rate or blood pressure in normal rats. Resveratrol infusion produced significant natriuresis at all doses, independent of hemodynamic responses, suggesting it may have a direct effect on renal tubular sodium handling independent of perfusion pressure, renal blood flow, or changes in renal vascular resistance. We hypothesized chronic ingestion of resveratrol would reduce Ang II-induced and fructose-induced salt-sensitive increases in blood pressure by decreasing sodium reabsorption through a NO-dependent mechanism. In both models of elevated blood pressure, resveratrol treatment did not blunt initial increases in blood pressure in either the Ang II or fructose-induced salt sensitive model nor did resveratrol increase sodium excretion or decrease sodium retention. However, following 3 weeks of treatment the increases in blood pressure began to reverse on the Ang II model, but not the fructose salt sensitive model (during 2 weeks of treatment). Resveratrol did not decrease oxidative stress, as measured by urinary excretion of 8-isoprostane, in either model. Notable, short term exposure to fructose (2 weeks), independent of blood pressure or salt, increased oxidative stress. It is well-defined from our data that resveratrol has distinct physiological actions on nitric oxide production, free radical formation, natriuresis, and sustained hypertension. However, the data does not suggest efficacy in prevention of hypertension.

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