EFFECTS OF THE INHIBITION OF NITRIC OXID SYNTHESIS IN THE HEMODYNAMICAND EXCRETORY FUNCTIONS OF RATS WITH BILIARY CIRRHOSIS

Liver cirrhosis is associated with elevated blood nitrid oxide (NO) le vels. In the present study we have evaluated the role of NO in the ren al hemodynamic and excretory abnormalities present in an experimental model of biliary cirrhosis. The experiments were performed in Munich-W istar rats, 25 days after bile duct ligation (BDL) or sham operation ( controls). Intravenous infusion of NO synthesis inhibitor (L-NAME, 1,5 and 10 mu g/Kg/min) did not alter mean arterial pressure (MAP) in con trol animals and decreased renal papillary blood flow (PBF, laser-dopp ler flowmetry) in a dose-dependent manner (5.4 +/- 1.6 %, 16.2 +/- 2.6 % and 26.3 +/- 3.3 %, respectively). In the BDL group, basal MAP was lower and increased significantly with the first dose of L-NAME (from 90.6 +/- 3.8 to 105.2 +/- 5.1 mmHg) and kept increasing with the follo wing doses (127.4 +/- 4.2 and 133.7 +/- 4.2 mmHg). In these BDL animal s, basal PBF was significantly lower (40.3 +/- 3.8 %) than that of the controls and, L-NAME administration induced higher increases in papil lary resistance than in the controls. In control animals prepared for renal clearances and subjected to the same infusion dosage, L-NAME adm inistration did not change MAP and slightly increased diuresis and nat riuresis only with the highest dose of the inhibitor. In contrast, in the BDL animals, MAP, diuresis and natriuresis increased significantly after infusion of the NO synthesis inhibitor ti-om the first dose and remained elevated throughout the experiment. Renal vasoconstriction i nduced by the NO synthesis inhibitor was also significantly greater in the BDL group. These results indicate that anesthetized rats with bil iary cirrhosis show a higher systemic and renal sensitivity to NO synt hesis inhibition. This result suggests that NO participates in the low er arterial pressure and renal alterations of the animals with biliary cirrhosis.