Cyclooxygenase 2 inhibition exacerbates AQP2 and pAQP2 downregulation independently of V2 receptor abundance in the postobstructive kidney

Abstract

The type 2 vasopressin receptor (V2R) and vasopressin‐regulated transport proteins is downregulated in postobstructive kidney. ANG II receptor (AT1R) blockade attenuates V2R, AQP2 and pAQP2 downregulation and partially reverses obstruction‐induced inhibition of cAMP generation. Furthermore, AT1R blockade attenuates cyclooxygenase 2 (COX2) induction and as COX2 inhibition attenuates AQP2 downregulation 3 days after release of bilateral ureteral obstruction (BUO) we speculated if the effects of AT1R blockade on V2R and the vasopressin‐regulated pathway are due to reduced prostaglandin E2 generation.Rats were subjected to 24h BUO followed by 48h release and treated with parecoxib, a specific COX2 inhibitor, or saline. Control rats were sham‐operated. Urine output, water intake, and solution free water clearance were comparable in parecoxib‐ and saline‐treated rats. Immunoblotting, revealed a significant decrease in AQP2 and pAQP2 abundance to 20% and 23% of sham levels in BUO+P rats compared to 40% and 55% of sham levels in saline‐treated BUO rats. V2R abundance decreased to less than 10% of sham in both BUO and BUO+P rats. Finally, vasopressin‐stimulated cAMP generation in inner medullary membrane fractions from BUO+P rats tended to be reduced compared to BUO rats.In conclusion, COX2 inhibition exacerbates AQP2 and pAQP2 downregulation 48h after release of 24 h BUO independently of V2R abundance