Endothelium-dependent vascular hyporesponsiveness without detection of nitric oxide synthase induction in aortas of cirrhotic rats.
Hepatology
; 22(6): 1856-62, 1995 Dec.
Article
em En
| MEDLINE
| ID: mdl-7489998
ABSTRACT
The present experiments were designed to test if induction of nitric oxide synthase (NOS) plays a role in the systemic vasodilation observed in hepatic cirrhosis. Because endotoxin levels are elevated in cirrhosis, and endotoxin stimulates inducible nitric oxide synthase (iNOS) expression in several cell lines, aortas of carbon tetrachloride-induced cirrhotic rats with ascites were evaluated for iNOS expression. Endotoxin-treated rats were studied as positive controls. Phenylephrine contraction was decreased in aortic rings with endothelium from both endotoxin-treated and cirrhotic rats as compared with controls. However, after endothelium denudation, the reduced contractility persisted in endotoxin-treated rats but disappeared in cirrhotic rats. L-Nitro-arginine-methylester (L-NAME), a nonselective inhibitor of NOS, potentiated the phenylephrine contraction of aortic rings with and without endothelium from endotoxin-treated rats but only rings with endothelium from cirrhotic rats. Moreover, aminoguanidine (AG), a preferential inhibitor of iNOS, did not affect phenylephrine contraction of rings with or without endothelium from cirrhotic rats but reversed the blunted response in endotoxin-treated rats. Northern analysis detected iNOS RNA (mRNA) expression in aortas of endotoxin-treated rats but did not detect it from cirrhotic rats. In summary, although several previous studies provide evidence for in vivo overproduction of nitric oxide in cirrhosis, the present results do not support iNOS induction as the source of nitric oxide in aortas of cirrhotic rats. Rather, because the aortic vascular hyporesponsiveness in cirrhosis is endothelium-dependent, overexpression or overstimulation of the endothelial constitutive isoform of NOS appears to be involved.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Óxido Nítrico Sintase
/
Cirrose Hepática Experimental
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Hepatology
Ano de publicação:
1995
Tipo de documento:
Article
País de afiliação:
Estados Unidos