RENAL EFFECTS OF NITRIC-OXIDE SYNTHESIS INHIBITION IN CIRRHOTIC RATS

In the present study, we have characterized the renal response to inhi bition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro -L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic r ats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effect s on water (UV) and sodium (UNaV) excretion in cirrhotic and control a nimals. Infusion of 1 mu g.kg(-1) min(-1) of L-NAME in CIR (n = 5) dec reased renal plasma flow (RPF) at the end of the 3-h period, whereas U V, UNaV, and glomerular filtration rate (GFR) were unaltered. In contr ast, infusion of L-NAME at 10 mu g.kg(-1).min(-1) in six more CIR incr eased UV and UN, significantly by the Ist h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 mu g.kg(-1).min(-1) in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These eff ects were prevented by pretreatment with L-arginine (0.1 mg.kg(-1).min (-1)) in another group of ASC infused with 1 mu g.kg(-1).min(-1) of L- NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhi bition of NO synthesis at nonpressor doses improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an imp ortant mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.