Disruption of cyclooxygenase‐2 prevents down‐regulation of cortical AQP2 and AQP3 in response to bilateral ureteral obstruction

Abstract

Previously, we demonstrated that bilateral ureteral obstruction (BUO) in rats was associated with increased cyclooxygenase type 2 (COX-2) expression in renal inner medulla (IM) and that selective COX-2 inhibition prevented downregulation of aquaporin 2 (AQP2) in response to BUO. We hypothesized that mice with disrupted COX-2 are protected from BUO-induced changes in transporters. COX-2 deficient and wild type littermates (COX-2−/− and WT C57BL/6J) were employed to determine aquaporin-2 and -3 and vasopressin V2 receptor protein level in response to BUO. The kidneys were removed and prepared for QPCR and immunoblotting analyses. Plasma osmolality and creatinine increased in both WT and COX-2−/− mice subjected to BUO. Plasma urea was increased in COX-2−/− mice compared to WT at baseline and in response to BUO. COX-2 protein level increased in WT mice in response to BUO and was not detectable in COX-2−/−. V2 receptor protein abundance was lower COX-2−/− mice compared to WT mice after BUO. Downregulation of AQP2 and AQP3 mRNA and protein was prevented in the cortex of COX-2−/− mice subjected to BUO. In IM, AQP2 and AQP3 protein level decreased in response to BUO in both COX-2−/− and WT mice compared to sham. In conclusion, disrupted COX-2 prevents down-regulation of AQP2 and AQP3 in response to BUO in cortex, but not in inner medulla, suggesting a differential regulation of AQP2 and -3 expression in the separate kidney zones.