The endothelial and non-endothelial mechanism responsible for attenuated vasoconstriction in cirrhotic XXXX .

@entity2835 @entity2871 @entity82 @entity35 @entity2872 @entity2918 @entity7293 @entity2647 @entity842 @entity1575 @entity3352
The pathogenesis of the vasodilatation associated with @entity1575 is not fully understood, but it has recently been postulated that it may be related to an increase in @entity842 production. The aim of this study was to compare the response of isolated aortic rings from normal and cirrhotic @entity35 to two vasoconstrictors, @entity2647 and @entity2872 , a @entity2871 analogue. @entity2835 was induced by ligation of the common bile duct; a sham operation was performed in control animals. Five weeks later, the aorta was removed and dissected into rings for study in organ chambers. Concentration-response curves were obtained for the two vasoconstrictors from rings with intact endothelium and from rings denuded of endothelium. We found that the vasoconstriction produced by @entity2647 was decreased in cirrhotic vessels both with and without endothelium, but the response to @entity2872 was not modified by @entity82 . Concentration-response curves for @entity2647 were also obtained from rings in which the synthesis of @entity842 and @entity2918 was inhibited by @entity7293 and @entity3352 , respectively. @entity842 synthase inhibition restored normal contractility of the rings with and without endothelium. This beneficial effect was not observed when cyclo-oxygenase activity was blocked with @entity3352 . This study suggests that cirrhotic vessels are hyporeactive to vasoconstrictors and that this effect is mediated through increased @entity842 production. The improvement observed after inhibition of the @entity842 pathway in denuded rings led us to suggest that @entity82 also induces @entity842 synthase in smooth muscle cells, as previously observed by others in septic animals.
