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. ? ? ?
| Jackson, Keith E; Jackson, Debra W; Quadri, Syed et al. (2011) Inhibition of heme oxygenase augments tubular sodium reabsorption. Am J Physiol Renal Physiol 300:F941-6 |
| Johnson, Fruzsina K; Johnson, Robert A; Durante, William et al. (2006) Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 290:R601-8 |
