Vascular hyporesponsiveness to endothelin 1 in rats with cirrhosis

Gastroenterology. 1994 Oct;107(4):1085-93. doi: 10.1016/0016-5085(94)90233-x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Blood Pressure / drug effects*
  • Dose-Response Relationship, Drug
  • Endothelins / pharmacology*
  • Glyburide / pharmacology
  • Hemodynamics / drug effects
  • Liver Cirrhosis, Experimental / physiopathology*
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Endothelins
  • Nitric Oxide
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Arginine
  • Glyburide
  • NG-Nitroarginine Methyl Ester