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Jørgen Frøkiær

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

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  • Department of Anatomy
  • Biomedical Radio Isotope Techniques
  • Institute of Clinical Medicine
  • The Department of Medicine and Nephrology C
Previously we demonstrated that ANG II receptor (AT1R) blockade attenuates V2 receptor (V2R), AQP2, and pS256-AQP2 downregulation in the postobstructed kidney and partially reverses obstruction-induced inhibition of cAMP generation and cyclooxygenase 2 (COX-2) induction. Therefore, we speculated whether the effects of AT1R blockade on V2R and the vasopressin-regulated pathway are attributable to attenuated COX-2 induction. To examine this, rats were subjected to 24-h bilateral ureteral obstruction (BUO) followed by 48-h release and treated with the COX-2 inhibitor parecoxib or saline. Control rats were sham-operated. Parecoxib treatment significantly reduced urine output 24 h after release of BUO whereas urine osmolality and solute-free water reabsorption was comparable between saline- and parecoxib-treated BUO rats. Immunoblotting revealed a significant decrease in AQP2 and pS256-AQP2 abundance to 20 and 23% of sham levels in parecoxib-treated BUO rats compared with 40 and 55% of sham levels in saline-treated BUO rats. Immunohistochemistry confirmed the exacerbated AQP2 and pS256-AQP2 downregulation in parecoxib-treated BUO rats. Finally, parecoxib treatment had no effect on V2R downregulation and the inhibited, vasopressin-stimulated cAMP generation in inner medullary membrane fractions from the postobstructed kidney. In conclusion, COX-2 inhibition exacerbates AQP2 and pS256-AQP2 downregulation 48 h after release of 24-h BUO independently of V2R abundance and vasopressin-stimulated cAMP generation. The results indicate that COX-2 inhibition does not mimic AT1R blockade-mediated effects and that AT1R-mediated AQP2 regulation in the postobstructed kidney collecting duct is independent of COX-2 induction.
Original languageEnglish
JournalAmerican Journal of Physiology: Renal Physiology
Volume298
Issue4
Pages (from-to)F941-50
ISSN1931-857X
DOIs
Publication statusPublished - 2010

    Research areas

  • Adenylate Cyclase, Animals, Aquaporin 2, Cyclooxygenase 2 Inhibitors, Down-Regulation, Isoxazoles, Kidney, Male, Phosphorylation, Rats, Rats, Sprague-Dawley, Receptors, Vasopressin, Reperfusion Injury, Sodium-Potassium-Chloride Symporters, Vasopressins

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