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 altered furosemide-sensitive sodium reabsorption in rats with liver cirrhosis induced by common bile duct ligation. CBL and sham-operated control animals were 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 all groups. Sodium balance studies showed that aldosterone receptor blockade prevented sodium retention in cirrhotic rats. Clearance studies showed that the glomerular 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.) produced significantly greater diuretic (+59%) and natriuretic (+56%) responses in CBL rats than in sham-operated controls. The urinary furosemide excretion rate (UFURV) reflects delivery of furosemide to the thick ascending limb. When the natriuresis was expressed relative to UFURV (i.e., the natriuretic efficiency), we found that natriuretic efficiency of furosemide was significantly increased in untreated CBL rats (+59%). However, the natriuretic efficiency of furosemide was normalized in CBL rats treated with canrenoate. The urinary excretion of furosemide was unchanged in untreated CBL rats, but it was significantly increased in cirrhotic rats treated with canrenoate (+43%). This suggests that in CBL rats, chronic canrenoate treatment increases the renal elimination of furosemide as a consequence of reduced metabolism. 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.
Jonassen
T E
TE
Department of Pharmacology, the Panu Institute, University of Copenhagen, Denmark. fitj@farmakol.ku.dk
Petersen
J S
JS
Sørensen
A M
AM
Andreasen
F
F
Christensen
S
S
D000818:Animals; D002191:Canrenoic Acid / Q000627:therapeutic use*; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000378:metabolism*; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000378:metabolism*
D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D012965:Sodium Chloride; D005665:Furosemide; D002191:Canrenoic Acid