Endothelium‐dependent dilation in coronary arterioles following chronic nitric oxide synthase inhibition

Abstract

This study tested the hypothesis that chronic inhibition of NOS with NG-nitro-L-arginine methyl ester (L-NAME) decreases endothelium-dependent dilation due to decreased NO release. Vasomotor reactivity of coronary arterioles isolated from 8 swine that were chronically administered L-NAME (8.3 ± 0.5 mg/kg/d) in their water for 30–90 days and 7 controls was examined. Arterioles isolated from the left ventricular apex were mounted on glass micropipettes and allowed to develop spontaneous tone. Dilation was produced by increasing doses of endothelium-dependent bradykinin (BK) and –independent sodium nitroprusside (SNP), performed in the presence and absence of L-NAME [300μM] in the bath. The relative contribution of NO release to the dilation was assessed by comparing dilation between arterioles with and without acute L-NAME treatment. BK and SNP dilation was similar in both groups. However, the relative contribution of NO release to BK-induced dilation (3 x 10−10 M, BK) was significantly decreased in the arterioles from pigs chronically treated with L-NAME (24±12 %) compared to arterioles from control pigs (62±11 %). These results suggest that endothelium-dependent dilation is maintained in coronary arterioles following chronic L-NAME inhibition of NOS activity, perhaps by compensatory increases in the release of non-NOS mediators. (NIH Grant #s RR-18276 and HL-52490).