M Hartleb1, R Moreau, S Cailmail, C Gaudin, D Lebrec. 1. Laboratoire d'Hémodynamique Splanchnique, Unité de Recherches de Physiopathologie Hépatique (INSERM Unité 24), Hôpital Beaujon, Clichy, France.
Abstract
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 (NG-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 micrograms/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 micrograms/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 micrograms/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.
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 (NG-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 micrograms/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 micrograms/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 micrograms/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.
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