Endothelin and vascular reactivity in cirrhosis

Background/Aims : Because the vasodilator nitric oxide is overproduced in cirrhosis, this substance may decrease pressor 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 : Pressor dose‐response curves to endothelin 1 (0.5, 1, 3, 6, and 10 μg/kg intravenously) were obtained in animals with or without pretreatment with L ‐NAME. Results : Pressor responses to endothelin 1 alone were significantly lower in cirrhotic than in normal rats. In cirrhotic animals, pressor responses to 3, 6, and 10 μg/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, pressor 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, pressor responses to 6 and 10 μg/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.