Decreased vasopressin-mediated renal water reabsorption in rats with chronic aldosterone-receptor blockade

Thomas E.N. Jonassen, Dominique Promeneur, Sten Christensen, Jørgen S. Petersen, Søren Nielsen

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have suggested that mineralocorticoids are needed for a normal action of vasopressin on collecting duct osmotic water permeability. However, the mechanisms behind this are unknown. To investigate if aldosterone-receptor blockade influences vasopressin type 2 receptor (V2)-mediated renal water reabsorption and the renal expression of the vasopressin-regulated water channel aquaporin-2 (AQP2), rats were treated with the aldosterone-receptor antagonist canrenoate (20 mg/day iv) for 4 wk. Daily urine flow was increased significantly by 44%, and urine osmolality was decreased by 27% in canrenoate-treated rats. Acute V2- receptor blockade (OPC-31260, 800 μg·kg-1·h-1) was performed under conditions in which volume depletion was prevented. In control rats, OPC- 31260 induced a significant increase in urine flow rate (V, +25%) and free water clearance (C(H2O), -29%). In canrenoate-treated rats, the effect of OPC-31260 was significantly reduced, and semiquantiative immunoblotting demonstrated a significant reduction (45%) in AQP2 expression. Because rats with common bile duct ligation (CBL) have a reduced vasopressin-mediated water reabsorption compared with normal rats (V: -24%; C(H2O): -28%, and 86% downregulation of AQP2), the effect of canrenoate combined with OPC- 31260 was tested. Canrenoate treatment of CBL rats significantly increased daily urine flow, decreased urine osmolality, and impaired the aquaretic response to OPC-31260 (V:-23%; C(H2O): -31%) with maintained suppression of the renal AQP2 expression. Thus canrenoate treatment of normal and CBL rats showed 1) increased urine production, 2) reduced aquaretic effect of acute V2-receptor blockade, and 3) a marked reduction in AQP2 expression. This strongly supports the view that aldosterone plays a significant role for vasopressin-mediated water reabsorption.

Original languageEnglish (US)
Pages (from-to)F246-F256
JournalAmerican Journal of Physiology - Renal Physiology
Volume278
Issue number2 47-2
DOIs
StatePublished - Feb 2000

Keywords

  • Aquaporin-2
  • Canrenoate
  • Cirrhosis
  • Collecting ducts
  • OPC-31260
  • V-receptor

ASJC Scopus subject areas

  • Physiology
  • Urology

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