[Renal effects of the chronic inhibition of nitric oxide synthesis in cirrhotic rats with ascites]

Nefrologia. 2001;21(6):556-64.
[Article in Spanish]

Abstract

Previous studies have shown that acute inhibition of nitric oxide (NO) synthesis improves sodium and water excretion and increases blood pressure in cirrhotic rats with ascites, thus suggesting that NO is an important factor contributing to the arterial hypotension and sodium retention of liver cirrhosis. In the present work we have analyzed the renal effects derived from the chronic oral treatment (10 days) with aminoguanidine (AG, 100 mg/kg/day), a preferential inhibitor of inducible NO synthase (iNOS), or Nw-Nitro-L-Arginine Methyl Ester (L-NAME, 0.5 mg/kg/day), a nonselective inhibitor of NOS, in an experimental model of liver cirrhosis with ascites (carbon tetrachloride inhalation). Untreated cirrhotic rats showed lower mean arterial pressure (MAP), diuresis, natriuresis and glomerular filtration rate (GFR) and similar renal blood flow (RBF) compared with the untreated control rats. Chronic administration of AG did not modify significantly any parameter in cirrhotic and control animals. Conversely, long-term L-NAME administration to cirrhotic rats normalized MAP and significantly increased water and sodium excretion, whereas in control animals these parameters were not significantly modified. These results show that chronic NO synthesis inhibition with L-NAME, but not with aminoguanidine, improves renal perfusion pressure and increases the lower sodium and water excretion of cirrhotic rats with ascites. Thus, an enhanced production of NO is an important factor contributing to the renal sodium and water retention characteristic of liver cirrhosis.

Publication types

  • Comparative Study
  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ascites
  • Blood Pressure / drug effects
  • Carbon Tetrachloride / toxicity
  • Diuresis / drug effects
  • Glomerular Filtration Rate / drug effects
  • Guanidines / pharmacology
  • Guanidines / therapeutic use*
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Liver Cirrhosis, Experimental / complications*
  • Liver Cirrhosis, Experimental / metabolism
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • NG-Nitroarginine Methyl Ester / therapeutic use*
  • Natriuresis / drug effects
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects

Substances

  • Guanidines
  • Nitric Oxide
  • Carbon Tetrachloride
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • pimagedine
  • NG-Nitroarginine Methyl Ester