VASCULAR HYPORESPONSIVENESS TO ENDOTHELIN-1 IN RATS WITH CIRRHOSIS

Background/Aims: Because the vasodilator nitric oxide is overproduced in cirrhosis, this substance may decrease presser responses to the vasoconstrictor endothelin 1. This study aimed to examine the effects of a NO synthesis inhibitor (N-G-nitro-L-arginine methyl ester; L-NAME) on vascular responsiveness to endothelin 1 in normal and cirrhotic rats. Methods: Presser dose-response curves to endothelin 1 (0.5, 1, 3, 6, and 10 mu g/kg intravenously) were obtained in animals with or without pretreatment with L-NAME. Results: Presser responses to endothelin 1 alone were significantly lower in cirrhotic than in normal rats. In cirrhotic animals, presser responses to 3, 6, and 10 mu g/kg of endothelin 1 were significantly higher in the presence than in the absence of L-NAME. The responses to the other doses of endothelin 1 were not affected by L-NAME. In normal rats, presser responses to all doses of endothelin 1 were significantly higher in the presence than in the absence of L-NAME. In animals pretreated with L-NAME, presser responses to 6 and 10 mu g/kg of endothelin 1 did not differ between cirrhotic and normal rats, whereas responses to other doses remained lower in cirrhotic than in normal rats. Conclusions: In rats with cirrhosis, NO seems to contribute to vascular hyporeactivity to high doses but not to low doses of endothelin 1.