Aldosterone receptor blockade inhibits increased furosemide-sensitive sodium reabsorption in rats with liver cirrhosis

We examined the role of chronic aldosterone receptor blockade on the altere d furosemide-sensitive sodium reabsorption in rats with liver cirrhosis ind uced by common bile duct ligation. CBL and sham-operated control animals we re treated with the aldosterone receptor antagonist canrenoate (20 mg/day i .v.) for 4 weeks. Untreated CBL and sham-CBL served as control groups. The plasma concentration of aldosterone was within the normal range in ail grou ps. Sodium balance studies showed that aldosterone receptor blockade preven ted sodium retention in cirrhotic rats. Clearance studies showed that the g lomerular filtration rate was unchanged, whereas the renal plasma flow was increased in CBL rats. A test dose of furosemide (7.5 mg/kg b.wt. i.v.) pro duced significantly greater diuretic (+59%) and natriuretic (+56%) response s in CBL rats than in sham-operated controls. The urinary furosemide excret ion rate (UFURV) reflects delivery of furosemide to the thick ascending lim b. When the natriuresis was expressed relative to UFURV (i.e., the natriure tic efficiency), we found that natriuretic efficiency of furosemide was sig nificantly increased in untreated CBL rats (+59%). However, the natriuretic efficiency of furosemide was normalized in CBL rats treated with canrenoat e. The urinary excretion of furosemide was unchanged in untreated CBL rats, but it was significantly increased in cirrhotic rats treated with canrenoa te (+43%). This suggests that in GEL rats, chronic canrenoate treatment inc reases the renal elimination of furosemide as a consequence of reduced meta bolism. These data suggest that chronic aldosterone receptor blockade with canrenoate prevents sodium retention in cirrhotic rats partly by inhibition of increased sodium reabsorption in the thick ascending limb.