Diminished adenylate cyclase activity and aquaporin 2 expression in acute renal failure rats

Background. The present study was aimed at investigating the changes of aqu aporin 2 (AQP2) expression and its underlying mechanisms in ischemic acute renal failure (ARF). Methods. ARF was induced by clamping the both renal arteries for 60 minutes in rats. Two or seven days later, AQP2 expression and trafficking were det ermined in the kidney by Western blot analysis and immunohistochemistry. Th e activity of adenylate cyclase was also measured. Results. The urinary flow rates in ARF-2 and ARF-7 day were significantly i ncreased in association with decreases of urine osmolality. While there was decreased expression of AQP2 in the cortex, outer medulla, and inner medul la in ARF, it was most pronounced in the outer medulla. The AQP2 expression was reduced in the apical membrane-enriched fraction as well the subapical vesicle-enriched fraction in ARF; however, the degree was greater in the f ormer than in the latter. Immunohistochemical study also showed a markedly decreased expression of AQP2 in the collecting duct in ARF. cAMP generation in response to arginine vasopressin (AVP) in the kidney was attenuated in ARF, most prominently in the outer medulla. cAMP generation in the outer me dulla in response to forskolin was not affected, but sodium fluoride was si gnificantly blunted in ARF. Conclusions. The AVP-stimulated adenylate cyclase activity is impaired in A RF, secondary to a defect at the level of the G protein. The expression of AQP2 was reduced as a consequence, which may in part account for urinary co ncentration defect in ARF.