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

We assessed the mechanisms of action of N-G-hydroxy-L-arginine in isolated pol cine large coronary arterial rings. Increasing (1, 10 and 100 mu M) concentrations of N-G-hydroxy-L-arginine evoked endothelium-dependent dilation which was eliminated by 100 mu M 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 mu M), 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 vias measured with a chemiluminescence analyser. A23187 (10 mu M), N-G-Hydroxy-L-arginine (100 mu M), and to a lesser extent N-G-hydroxy D-arginine (100 mu M), 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 lending 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.