HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1322    most recent 00394.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nørregaard, R. Articles by Frøkiær, J. Search for Related Content PubMed PubMed Citation Articles by Nørregaard, R. Articles by Frøkiær, J.

COX-2 activity transiently contributes to increased water and NaCl excretion in the polyuric phase after release of ureteral obstruction

¹The Water and Salt Research Center, ²Institute of Clinical Medicine, ³Institute of Anatomy, University of Aarhus, ⁶Department of Clinical Physiology and Nuclear Medicine, Aarhus University Hospital-Skejby, Aarhus; and ⁴Department of Physiology and Pharmacology, University of Southern Denmark, Odense, Denmark; ⁵Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; and ⁷Department of Pediatrics, Philipps University, Marburg, Germany

Submitted 5 October 2006 ; accepted in final form 12 January 2007

Release of bilateral ureteral obstruction (BUO) is associated with reduced expression of renal aquaporins (AQPs), polyuria, and impairment of urine-concentrating capacity. Recently, we demonstrated that 24 h of BUO is associated with increased cyclooxygenase (COX)-2 expression in the inner medulla (IM) and that selective COX-2 inhibition prevents downregulation of AQP2. In the present study, we tested the hypothesis that COX-2 activity increases in the postobstructive phase and that this increase in COX-2 activity contributes to polyuria and impaired urine-concentrating capacity. We examined the effect of the selective COX-2 inhibitor parecoxib (5 mg·kg^–1·day^–1 via osmotic minipumps) on renal functions and protein abundance of AQP2, AQP3, Na-K-2Cl cotransporter type 2 (NKCC2), and Na-K-ATPase 3 days after release of BUO. At 3 days after release of BUO, rats exhibited polyuria, dehydration and urine and IM tissue osmolality were decreased. There were inverse changes of COX-1 and COX-2 in the IM: COX-2 mRNA, protein, and activity increased, while COX-1 mRNA and protein decreased. Parecoxib reduced urine output 1 day after release of BUO, but sodium excretion and glomerular filtration rate were unchanged. Parecoxib normalized urinary PGE₂ and PGI₂ excretion and attenuated downregulation of AQP2 and AQP3, while phosphorylated AQP2 and NKCC2 remained suppressed. Parecoxib did not improve urine-concentrating capacity in response to 24 h of water deprivation. We conclude that decreased NKCC2 and collapse of the IM osmotic gradient, together with suppressed phosphorylated AQP2, are likely causes for the impaired urine-concentrating capacity and that COX-2 activity is not likely to mediate these changes in the chronic postobstructive phase after ureteral obstruction.

cyclooxygenase; ureteral obstruction; PGE₂; parecoxib; AQP2; NKCC2; urine-concentrating capacity

This article has been cited by other articles:

				A. M. Jensen, E. H. Bae, R. A. Fenton, R. Norregaard, S. Nielsen, S. W. Kim, and J. Frokiaer Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction Am J Physiol Renal Physiol, January 1, 2009; 296(1): F127 - F134. [Abstract] [Full Text] [PDF]

				M. H. M. Shimizu, A. Danilovic, L. Andrade, R. A. Volpini, A. B. Liborio, T. R.C. Sanches, and A. C. Seguro N-acetylcysteine protects against renal injury following bilateral ureteral obstruction Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3067 - 3073. [Abstract] [Full Text] [PDF]