Oxidative metabolism and its possible modulation by nitric oxide (NO) was examined in endothelial-intact and endothelial-denuded segments of porcine carotid arteries. Endothelial-intact arteries displayed appropriate NO-mediated vasorelaxation to acetylcholine (ACh). Endothelial-denuded arteries demonstrated absent vasorelaxation to ACh stimulation and depressed contractile responsiveness to K + depolarization, which was normalized by inhibition of NO synthesis by N ω -nitro-l-arginine methylester (l-NAME). Confirmation that carotid arteries continued to produce NO despite removal of the endothelium was indicated by detection of NO metabolites in the incubation medium bathing the arteries. O 2 consumption and the oxidation of glucose and fatty acid were depressed in endothelial-denuded arteries. Depression of O 2 consumption and glucose oxidation was completely reversed by treatment with l-NAME. We conclude that endogenous NO produced by non-endothelial vascular cells depresses contractility, O 2 consumption, and oxidation of energy substrates in vascular smooth muscle. The endothelium may play a role in oxidative metabolism of vascular smooth muscle possibly by modulating the effects of NO produced by other cells of the vessel wall, or by other factors.