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

Previous studies have suggested that mineralocorticoids are needed for a no rmal action of vasopressin on collecting duct osmotic water permeability. H owever, the mechanisms behind this are unknown. To investigate if aldostero ne-receptor blockade influences vasopressin type 2 receptor (V-2)-mediated renal water reabsorption and the renal expression of the vasopressin-regula ted water channel aquaporin-2 (AQP2), rats were treated with the aldosteron e-receptor antagonist canrenoate (20 mg/day iv) for 4 wk. Daily urine flow was increased significantly by 44%, and urine osmolality was decreased by 2 7% in canrenoate-treated rats. Acute V-2-receptor blockade (OPC-31260, 800 mu g.kg(-1).h(-1)) was performed under conditions in which volume depletion was prevented. In control rats, OPC-31260 induced a significant increase i n urine flow rate (V, +25%) and free water clearance (CH2O, -29%). In canre noate-treated rats, the effect of OPC-31260 was significantly reduced, and semiquantiative immunoblotting demonstrated a significant reduction (45%) i n 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 df canre noate combined with OPC-31260 was tested. Canrenoate treatment of CBL rats significantly increased daily urine flow, decreased urine osmolality, and i mpaired the aquaretic response to OPC-31260 (V: -23%; C-H2O: -31%) with mai ntained suppression of the renal AQP2 expression. Thus canrenoate treatment of normal and CBL rats showed 1) increased urine production, 2) reduced aq uaretic effect of acute V-2-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.