DOSES OF ENDOTHELIN HAVE NATRIURETIC EFFECTS IN CONSCIOUS RATS WITH CIRRHOSIS AND ASCITES

MAP, RPF, GFR, V and U(Na)V were measured in nine conscious control and in 11 conscious cirrhotic rats with ascites before and following two bolus injections (100 and 600 pmol/kg body wt) of endothelin (ET). PRA and plasma concentration of aldosterone and ANP were measured in basal conditions and following the high dose ET. ET induced similar increase in MAP and decrease in RPF and GFR in control and cirrhotic rats. High-dose ET produced a significant reduction in U(Na)V in control rats (from 2.22 +/- 0.46 to 1.14 +/- 0.28-mu-Eq/min, P < 0.01). By contrast, it induced marked natriuresis in cirrhotic rats (from 0.76 +/- 0.18 to 2.31 +/- 0.70-mu-Eq/min, P < 0.05). ET significantly increased aldosterone (control rats: 59.3 +/- 2.2 vs. 85.4 +/- 7.4 ng/dl, P < 0.025; cirrhotic rats: 115.0 +/- 15.8 vs. 163.9 +/- 30.8, ng/dl, P < 0.05) and ANP (control rats: 20.1 +/- 3.4 vs. 42.7 +/- 7.7, fmol/ml, P < 0.025) and significantly suppressed PRA (control rats: 2.5 +/- 0.5 vs. 0.2 +/- 0.04, ng/ml.hr, P < 0.025; cirrhotic rats: 16.6 +/- 2.9 vs. 5.0 +/- 1.1, ng/ml.hr, P < 0.01) in both groups of animals, These results indicate that ET has marked natriuretic properties in cirrhosis with ascites due to inhibition of tubular sodium reabsorption.