Effects of chronic nitric oxide synthase inhibition on endothelium-dependent and -independent relaxation in arteries that perfuse skeletal muscle of swine

The purpose of this investigation was to test the hypothesis that chronic N-G-nitro-L-arginine methyl ester (L-NAME) treatment produces differential effects on conduit artery and resistance arteriole relaxation responses to endothelium-dependent and -independent vasodilators in arteries that perfuse skeletal muscle of swine. To test this hypothesis, conduit skeletal muscle arteries and second-order skeletal muscle (2A) arterioles were harvested from 14 Yucatan swine that were chronically administered L-NAME and from 16 controls. In vitro assessments of vasorelaxation to increasing doses of acetylcholine (ACH), bradykinin (BK), and sodium nitroprusside (SNP) were performed in both conduit and 2A arterioleS. L-NAME treatment produced a significant reduction in both BK and ACH relaxation responses in the conduit arteries. In contrast, the relaxation response and/or sensitivity to SNP were significantly greater in the intact, but not denuded, conduit arterial rings from chronically L-NAME-treated swine. There were no significant effects of chronic L-NAME treatment on vasodilation of skeletal muscle arterioles. These findings suggest (1) that unlike arterioles, skeletal muscle conduit arteries do not functionally compensate for a lack of NO through the upregulation of alternative vasodilator pathways; (2) that the greater relaxation response in conduit arteries of chronically L-NAME-treated swine to SNP can be explained by alterations to the endothelium.