Mechanisms mediating the vasodilatory effects of N-hydroxy-L-arginine in coronary arteries.
We assessed the mechanisms of action of NG-hydroxy-L-arginine in isolated porcine large coronary arterial rings. Increasing (1, 10 and 100 microM) concentrations of NG-hydroxy-L-arginine evoked endothelium-dependent dilation which was eliminated by 100 microM of NG-nitro-L-arginine methyl ester, but not affected by a cytochrome P450 inhibitors (miconazole or 7-ethoxyresorufin). At a given concentration, the dilatory response to NG-hydroxy-L-arginine was stronger than that elicited by L-arginine. NG-Hydroxy-L-arginine (100 microM), but not NG-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 microM), NG-Hydroxy-L-arginine (100 microM), and to a lesser extent NG-hydroxy-D-arginine (100 microM), significantly increased NO concentration over 15 min observation period. When A23187 and NG-hydroxy-L-arginine were combined, NO concentration increased in an additive fashion. Enhanced NO release by either A23187, NG-hydroxy-L-arginine or NG-hydroxy-D-arginine was attenuated by NG-nitro-L-arginine methyl ester. We conclude that NG-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 P450 were not involved the dilatory response to NG-hydroxy-L-arginine. In this respect, porcine coronary arteries differ significantly from cultured smooth muscle cells in metabolising NG-hydroxy-L-arginine.
Abdul-Hussain
M N
MN
Critical Care Division, Royal Victoria Hospital, Montreal, Quebec, Canada.
Jia
Y L
YL
Hussain
S N
SN
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects*; D066298:In Vitro Techniques; D008825:Miconazole / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D010078:Oxazines / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology*
D010078:Oxazines; D014665:Vasodilator Agents; D009569:Nitric Oxide; D000001:Calcimycin; C068309:N(omega)-hydroxyarginine; C007649:ethoxyresorufin; D008825:Miconazole; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester