In Vitro Alteration of Aortic Vascular Reactivity in Hypertension Induced by Chronic N G -Nitro- l -Arginine Methyl Ester

Abstract

Chronic administration of N G -nitro- l -arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I–converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME–induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME–treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside–induced dilation was increased in both L-NAME– and L-NAME plus quinapril–treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K + (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF 4 − , and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside–induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF 4 − , K + , and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530±120 fmol/mg protein, n=12, P <.05) and L-NAME plus quinapril (461±140 fmol/mg protein, n=12, P <.05) compared with controls (1798±522 fmol/mg protein, n=12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME–treated rats.