Question: 

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.

Methodology: 

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 abundance in response to BUO The kidneys were removed and prepared for QPCR, immunoblotting and immunohistochemical analyses.

Results: 

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. This was confirmed by immunohistochemistry.

Conclusion: 

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 zone.