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.