TIME RELATIONSHIPS BETWEEN PORTAL-HYPERTE NSION, DECREASE IN SODIUM-EXCRETION, AND ACTIVATION OF THE RENIN-ANGIOTENSIN SYSTEM IN RATS WITH EXPERIMENTAL BILIARY-CIRRHOSIS

1) To evaluate the biochemical, renal, histological and splanchnic and systemic hemodynamic abnormalities induced by bile duct obstruction i n rats, and 2) to study the temporal relationships between the start o f portal hypertension, decrease of urinary sodium excretion and activa tion of the renin-angiotensin system. Methods. Bile duct obstruction w as induced in 127 male Wistar rats, and renal function, hemodynamic bi ochemical and liver histology were evaluated at weeks 1, 2, 3 and 4 af ter complete bile duct obstruction; the data were compared to that in 30 control rats. Results. Portal pressure significantly increased at w eek 1 (11.7 +/- 1.5. vs. 7.8 +/- 1.5 mmHg, p < 0.05) while the mean ar terial pressure remained stable until week 4 when a slight decrease wa s observed (91.3 +/- 6.6 vs. 96.1 +/- 8.6 mmHg in control rats). A sig nificant decrease in urinary sodium excretion was observed at week 1 ( 1.1 +/- 0.5 mEq/24 h) compared to control rats (2.3 +/- 0.6 mEq/24 h). In addition, hyperreninemia was observed at week 1 (5.1 +/- 0.2 vs. 2 .4 +/- 1.3 ng Ang I/mL/h, p < 0.05) and hyperaldosteronism at week 2 ( 103 +/- 46 vs. 211 +/- 8.8 ng/24 h, p < 0.05) compared to control rats . Conclusion. A temporal relationship between the begining of portal h ypertension and a decrease of renal sodium excretion, hyperreninemia a nd hyperaldosteronism was observed in bile duct ligated rats. This exp erimental model could be used to evaluate the effects of new drugs to prevent biliary cirrhosis including the abnormalities in the renal han dling of sodium.