Mechanisms mediating the vasodilatory effects of N-hydroxy- l-arginine in coronary arteries

Abstract

We assessed the mechanisms of action of N G-hydroxy- l-arginine in isolated porcine large coronary arterial rings. Increasing (1, 10 and 100 μM) concentrations of N G-hydroxy- l-arginine evoked endothelium-dependent dilation which was eliminated by 100 μM of N G-nitro- l-arginine methyl ester, but not affected by a cytochrome P 450 inhibitors (miconazole or 7-ethoxyresorufin). At a given concentration, the dilatory response to N G-hydroxy- l-arginine was stronger than that elicited by l-arginine. N G-Hydroxy- l-arginine (100 μM), but not N G-hydroxy- d-arginine, potentiated the endothelium-dependent dilation of calcium ionophore A23187 but had no effect on endothelium-independent dilation evoked by an NO donor. NO release by endothelium-intact porcine coronary arterial rings was measured with a chemiluminescence analyser. A23187 (10 μM), N G-Hydroxy- l-arginine (100 μM), and to a lesser extent N G-hydroxy- d-arginine (100 μM), significantly increased NO concentration over 15 min observation period. When A23187 and N G-hydroxy- l-arginine were combined, NO concentration increased in an additive fashion. Enhanced No release by either A23187, N G-hydroxy- l-arginine or N G-hydroxy- d-arginine was attenuated by N G-nitro- l-arginine methyl ester. We conclude that N G-hydroxy- l-arginine exerts its effects on the contractility of coronary arteries by acting as a substrate for the endothelial nitric oxide synthase leading to enhanced NO production. Cytochrome P 450 were not involved the dilatory response to N G-hydroxy- l-arginine. In this respect, porcine coronary arteries differ significantly from cultured smooth muscle cells in metabolising N G-hydroxy- l-arginine.