Angiotensin II regulates Aquaporin 2 expression after bilateral ureteral obstruction in rats

Objective To investigate the regulation of angiotensin Ⅱ on the expression of Aquaporin 2 (AQP2) and renal function after bilateral ureteral obstruction (BUO). Methods Tweentyfour Munich-Wistar rats were randomly divided into three groups (BUO, n = 8; CAN n = 8; Sham n =8). The BUO (and BUO + CAN) model was built by bilateral ureteral ligation, then the osmotic minipumps contained isotonic saline (n = 8) or candesartan (n = 8) were implanted subcutaneously.Age-and time-matched sham-operated controls (n = 8) were prepared and observed in parallel. The rats were monitored for another 48 h after the 24 h BUO was released. The blood samples were collected and kidneys were harvested to examine the effects of angiotensin Ⅱ receptor antagonist candesartan on the dysregulation of AQP2 by semi quantitative immunoblottling. Results Release of BUO resulted in a marked polyuria(BUO vs. Sham: 92 ± 7 vs. 25 ± 3μl min 1 kg-1 ,n = 8;P＜0. 05) and a reduced urine osmolality(BUO vs. Sham: 636 ± 55 vs. 1 853 ± 163 mosmol/kgH2O,n = 8; P＜0. 05) ,which persisted throughout the experimental period. Administration of candesartan partly prevented this increase in postobstructive urine production (55 ± 5 vs. 92 ± 7 μl min-1 kg 1, n = 8 ; P＜0. 05) and decrease in urine osmolality (783 ±47 vs. 636 ± 55 mosmol kgH2O-1 ,n = 8; P＜0. 05). BUO induced a significantly increase in plasma osmolality (336 ± 10 vs. 303 ± 7 mosmol/kgH2O,n = 8; P＜0. 05) and plasma aldosterone concentration (4. 1 ±0. 2 vs. 1.4±0. 1 nmol L-1 ,n= 8; P＜0. 05) in BUO vs. In shamoperated control rats. Candesartan partly attenuated the increase of plasma aldosterone (2. 8 ± 0. 5 vs.4. 1 ± 0. 2 nmol L-1, n = 8; P＜0. 05). BUO resulted in a significantly decreased expression of AQP2compared with control,and candesartan prevented the reduction of AQP2 (P＜0. 05). Conclusions Angiotensin Ⅱ receptor antagonist prevents dysregulation of AQP2 in response to BUO. Angiotensin Ⅱ is involved in the pathophusilogical changes in renal function after release of BUO. Key words: Bilateral ureteral obstruction;  Aquaporin 2;  Angiotensin Ⅱ type I receptor blockers