RENIN AND ANGIOTENSINOGEN MESSENGER-RNA EXPRESSION IN THE KIDNEYS OF RATS SUBJECTED TO LONG-TERM BILE-DUCT LIGATION

Activation of antinatriuretic systems such as the renin-angiotensin sy stem, is of major importance in the pathogenesis of sodium retention i n cirrhosis. In this study, we studied the intrarenal renin angiotensi n system by measuring renin and angiotensinogen mRNA expression in the kidney of rats subjected to long-term bile duct ligation in a phase b efore the development of ascites, when sodium retention is already pre sent. Experiments were performed in sham-operated and bile duct-ligate d rats 3 wk after surgery. Balance studies showed lower sodium excreti on and greater sodium retention in the bile duct-ligated rats compared with the control animals. Plasma renin activity (4.41 +/- 1.01 ng Ang iotensin I/ml/hr in the bile duct-ligated group vs, 4.20 +/- 0.74 in t he controls) and plasma renin concentration were not different between the two groups. However, plasma renin substrate was significantly dec reased in bile duct-ligated animals. Total kidney renin mRNA was signi ficantly higher in the bile duct-ligated animals (0.83 +/- 0.14 densit ometric units vs. 0.44 +/- 0.04 in the controls), as determined on Nor thern-blot analysis and densitometric quantitation. Angiotensinogen mR NA expression in the kidneys of bile duct-ligated rats was significant ly decreased (0.09 +/- 0.01 densitometric units) compared with that of the controls (0.21 +/- 0.03). These results indicate that sodium-reta ining, nonascitic bile duct-ligated rats show abnormalities of the int rarenal renin angiotensin system that precede changes in plasma renin activity. Our data suggest that the intrarenal renin angiotensin syste m may participate in the initiation of the renal pathophysiological ab normalities present in bile duct-ligated rats.