Diminished expression of aquaporin water channels in ureteral-obstructed kidney in rats

Objective: We investigated whether regulation of aquaporin (AQP) water channels is altered in the ureteral-obstructed kidney. Material and Methods: Male Sprague-Dawley rats were unilaterally obstructed of their left proximal ureters for 48 h. The protein expression of AQP1-3 channels was determined in the kidney by Western blot analysis. The expression of AQP2 was also determined by immunohistochemistry. In order to specifically determine primary impairment of the pathway leading to an altered regulation of AQP channels stimulated by the arginine vasopressin (AVP)/cyclic adenosine monophosphate (cAMP) pathway, the catalytic activity and protein expression of different parts of the adenylyl cyclase complex were separately determined. Results: In the previously obstructed kidney, urinary osmolality and free water reabsorption were greatly decreased. The expression of AQP2 proteins was decreased in the cortex, outer medulla and inner medulla. Immunohistochemistry also showed a marked decrease in AQP2 expression. The expression of AQP1 and AQP3 was decreased in the outer medulla and inner medulla. cAMP generation in response to AVP, sodium fluoride or forskolin was greatly decreased. The expression of Gsalpha and adenylyl cyclase VI proteins was decreased. The contralateral kidney showed minimal or no changes in these parameters. Conclusions: The reduced abundance of AQP water channels may at least partly account for the urinary concentration defect in the ureteral-obstructed kidney. The primary point of impairment of AQP channels regulated by the AVP/cAMP pathway may lie at the level of the catalytic unit of adenylyl cyclase.