Effects of Candesartan on Na-K-2Cl cotransporter 2 in response to bilateral ureteral obstruction

Abstract

Objective To investigate the effects of candesartan (CAN) on dysregulation of Na-K-2Cl cotransporter 2 (NKCC2) and renal function in response to bilateral ureteral obstruction (BUO).Methods Thirty Munich-Wistar rats were randomly divided into three groups ( BUO,BUO + CAN and sham).The BUO model was built by bilateral uretersl ligation,then the BUO + CAN rats were treated with CAN.The kidneys were harvesmd for semi-quantitative immunoblotting.Results BUO induced an increase in plasma osmolality [BUO vs.sham:(340 ± 8 ) vs.(305 ± 9 ) mosmol/kg H2O,P ＜0.05 ]and plasma aldosterone concentration [ BUO vs.sham:(4.5 ±0.2) vs.( 1.4 ±0.1 ) nmol/L,P ＜0.05 ]in BUO vs.sham group.Administration of CAN partly prevented this increase in postobstructive urine production [ BUO + CAN vs.BUO:(60 ±7) vs.(99 ±6) μl/(min·kg),P ＜0.05],increase of urine Na [BUO+CAN vs.BUO:(4.9±0.4) vs.(7.0±0.7) μmol/(min·kg),P＜0.05]and decrease in urine osmolality [ BUO + CAN vs.BUO:( 806 ± 61 ) vs.( 647 ± 57 ) mosmol/kg H2O,P ＜ 0.05 ].CAN attenuated partly the increase of plasma osmolality and aldosterone [ BUO + CAN vs.BUO:(325 ±7) vs.(340±8) mosmol/kg H2O and (2.9±0.4) vs.(4.5 ±0.2) nmol/L,P＜0.05].BUO resulted in a significantly decreased expression of NKCC2 compared with sham group,and CAN prevented the reduction of NKCC2 (P ＜ 0.05).Conclusion Angiotensin Ⅱ receptor antagonist prevents dysregulation of NKCC2 in response to BUO,which is likely to contribute to the associated urinary concentrating defect. Key words: Ureteral obstruction; Cotransporter; Angiotensin Ⅱ receptor antagonist