Mechanisms mediating the vasodilatory effects of N-hydroxy-L-arginine in coronary arteries.
Eur J Pharmacol
; 305(1-3): 155-61, 1996 Jun 03.
Article
em En
| MEDLINE
| ID: mdl-8813546
ABSTRACT
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.
Buscar no Google
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina
/
Vasodilatadores
/
Vasos Coronários
Limite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Canadá