Increased nitric oxide-dependent vasorelaxation in aortic rings of cirrhotic rats with ascites

Hepatology. 1994 Dec;20(6):1615-21. doi: 10.1002/hep.1840200635.

Abstract

To assess whether aortic vessels of rats with cirrhosis and ascites possess an enhanced vascular response to endothelium-derived, nitric oxide-dependent vasodilators, we performed relaxation studies in isolated aortic rings of 21 control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites. We carried out studies after contracting the vessels with norepinephrine. We measured endothelium-dependent vasodilator response by administering increasing concentrations of acetylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(-4) mol/L). We evaluated endothelium-independent response by giving increased concentration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal absolute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75 mg) rings. Dose-response curves for endothelium-dependent vasodilators were shifted to the left in aortic rings of cirrhotic rats, and EC50 for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42 +/- 0.16 mumol/L, p < 0.025 and p < 0.01, respectively) than in control rings (1.91 +/- 0.33 mmol/L and 3.09 +/- 0.82 mumol/L). In both acetylcholine- and ADP-stimulated vessels, differences between cirrhotic and control rings disappeared after nitric oxide synthesis inhibition with N omega-nitro-L-arginine (10(-4) mol/L). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time enhanced in vitro vascular responsiveness to nitric oxide-dependent vasodilators in rats with cirrhosis and ascites, giving further support to the concept that nitric oxide activity is increased in cirrhosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adenosine Diphosphate / pharmacology
  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Analysis of Variance
  • Animals
  • Aorta / drug effects
  • Aorta / physiopathology*
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Ascites / etiology
  • In Vitro Techniques
  • Liver Cirrhosis, Experimental / complications
  • Liver Cirrhosis, Experimental / physiopathology*
  • Male
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase
  • Nitroarginine
  • Norepinephrine / pharmacology
  • Rats
  • Rats, Wistar
  • Regression Analysis
  • Sodium Nitrite / pharmacology
  • Vasodilation* / drug effects

Substances

  • Nitroarginine
  • Nitric Oxide
  • Adenosine Diphosphate
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • Sodium Nitrite
  • Acetylcholine
  • Norepinephrine