Abstract
Angiotensin II (AngII) induction is a well established model of hypertension with associated enhanced oxidative stress and increase in heme oxygenase activity. Vascular and renal tissues express heme oxygenase, which metabolizes heme to form biliverdin, free iron, and carbon monoxide (CO). CO has been demonstrated to relax vascular smooth muscle and to inhibit nitric oxide synthase. The current study examines the potential of the heme‐heme oxygenase carbon monoxide system to regulate acute AngII mediated increases in blood pressure. In vivo studies were conducted on Inactin anesthetized male Sprague Dawley rats (250–300g) on normal and high Zinc (1mM) diets. A dose response to AngII (5, 10, 20, 25ng/Kg, IV) was conducted to maintain a sustained elevation in blood pressure for an hour and half experimental period. Hemodynamic function was examined before and after acute administration of an inhibitor of CO production, zinc protoporphyrin‐IX (ZnPP; 30μmol/Kg, IV), a precursor for CO production, delta‐aminolevulinic acid (DALA; 40μmol/Kg, IV) or vehicle during AngII co‐infusion. A dose of 5ng/Kg AngII was observed to produce a 30mmHg sustained increase in blood pressure. In AngII hypertensive animals, ZnPP co‐infusion significantly attenuated the AngII increase in blood pressure. DALA or vehicle co‐infusion with AngII had no significant effects on the AngII mediated increase in blood pressure. In animals fed a high Zinc diet for 2 weeks, AngII infusion did not significantly increase blood pressure. This study demonstrates that an inhibitor of CO production can significantly attenuate the AngII mediated increase in blood pressure, while a precursor of CO production had no significant effects.Support: NIH F32 HL76001
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