Impaired responsiveness to angiotensin II in experimental cirrhosis: role of nitric oxide

Hepatology. 1993 Aug;18(2):367-72.

Abstract

Impaired vascular responsiveness to angiotensin II is a common feature in human cirrhosis with ascites. The aim of this study was to investigate whether vascular reactivity to angiotensin II is also decreased in rats with carbon tetrachloride-induced cirrhosis and ascites and to assess the role of endogenous nitric oxide in this abnormality. Increasing doses of angiotensin II (from 31 to 500 ng.kg-1.min-1) induced significantly smaller increases in total peripheral resistance in conscious cirrhotic rats with ascites (n = 8) than in control animals (n = 9) at each dose tested. A reduced response to angiotensin II was also observed in vitro in aortic rings of rats with cirrhosis and ascites compared with that in control aortic rings (maximal response: 104 +/- 16 mg vs. 204 +/- 18 mg; p < 0.001). This in vitro hyporesponsiveness to angiotensin II in aortic rings of cirrhotic rats with ascites was reversed on endothelium denudation or nitric oxide synthesis inhibition with N omega-nitro-L-arginine but was not influenced by cyclooxygenase inhibition with indomethacin. In conclusion, this study shows reduced vascular reactivity to angiotensin II in carbon tetrachloride-induced cirrhosis with ascites and indicates that this abnormality is mediated by nitric oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Aorta / drug effects*
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Hemodynamics / drug effects
  • In Vitro Techniques
  • Liver Cirrhosis, Experimental / physiopathology*
  • Male
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Nitroarginine
  • Rats
  • Rats, Wistar

Substances

  • Angiotensin II
  • Nitroarginine
  • Nitric Oxide
  • Arginine