NO AND EICOSANOID MEDIATE RENAL EFFECTS OF AT2 RECEPTORS

University Of Virginia Charlottesville, Charlottesville VA

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Abstract

DESCRIPTION (Adapated from the Principal Investigator's Abstract): Two types of angiotensin II receptors, AT1 and AT2, have been described. The majority of studies suggest that the renal actions of angiotensin II are mediated by angiotensin AT1 receptors. The physiologic actions of angiotensin II at the AT2 receptor have been difficult to elicit. Preliminary studies suggest that AT1 and AT2 have mutually counteracting hemodynamic effects. Dr. Siragy has utilized a novel renal interstitial microdialysis technique to evaluate the hypothesis that renal AT2 receptor physiologically modulates the renal production of bradykinin, nitric oxide and eicosanoids. The specific aims for this proposal are: 1) To test the hypothesis that AT2 receptor modulates renal production of bradykinin and nitric oxide. 2) To test the hypothesis that AT2 receptor influences renal eicosanoids through modulation of prostaglandin E 9-ketoreductase and nitric oxide generation. The proposed studies are related to the long term goal of increased understanding of the pathophysiology of body sodium and water excretion abnormalities and hypertension.