Carbon monoxide in AngII dependent hypertension

Tulane University Of Louisiana, New Orleans LA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Enzymatic degradation of heme by HO yields carbon monoxide (CO). CO relaxes vascular smooth muscle. These studies will test the hypothesis that HO-mediated CO production is increased during Angll induced hypertension, and it contributes to partial protection of renal hemodynamic and cardiovascular function. Specific Aims: 1) Determine if endogenous CO induced diuresis/natriuresis, increased cardiac output and decreased calculated renal vascular resistance is acutely or chronically enhanced by HS diet in normotensive and Angll-induced hypertensive rats. 2) Determine cardiovascular and renal HO protein expression and its alterations by the oxidative stress pathway in Angll induced hypertensive rats on highland low-salt diets. Methods: Renal/Systemic hemodynamic, excretory, and histological parameters will be evaluated in anesthetized acutely and in awake chronically instrumented normotensive and Angll infused hypertensive rats. CO system wills altered by administration of a heme precursor, DALA, and a HO inhibitor, ZnPP. Objectives: These studies will establish the role of the HO-CO system in the Angll induced hypertension. This knowledge may lead to novel therapeutic strategies for treating hypertension. [unreadable] [unreadable] [unreadable]