Cyclooxygenase-2 Inhibitor Preserves Medullary Aquaporin-2 Expression and Prevents Polyuria After Ureteral Obstruction
| Title: | Cyclooxygenase-2 Inhibitor Preserves Medullary Aquaporin-2 Expression and Prevents Polyuria After Ureteral Obstruction |
|---|---|
| Authors: | Cheng, Xu; Zhang, Hongyu; Lee, Hyung-Lae; Park, John M. |
| Publisher: | The Journal of Urology |
| Date Published: | December 01, 2004 |
| Reference Number: | 678 |
PURPOSE: Renal obstruction causes impairment of urinary concentrating ability, partly by decreasing aquaporin-2 (AQP-2) water channel level in the collecting ducts. We reported previously that ureteral obstruction induced cyclooxygenase-2 (COX-2) in the medullary collecting duct cells by increased mechanical stretch. In this study we investigated whether AQP-2 decrease after obstruction was regulated by COX-2. MATERIALS AND METHODS:: Sprague-Dawley rats were subjected to bilateral ureteral obstruction for 24 to 48 hours. During obstruction rats were given NS398, a COX-2 specific inhibitor, by oral gavage (2 mg/kg per day). COX-2 and AQP-2 levels were assessed in the inner medulla using Western blot. Urine output was measured after releasing obstruction to assess the degree of polyuria. RESULTS:: With obstruction COX-2 protein levels increased and AQP-2 levels decreased in the inner medulla. Corresponding to the loss of AQP-2, urine output increased 4.2-fold after obstruction. The obstructed rats receiving NS398 exhibited significant preservation of AQP-2 level (72% of control), as well as significant normalization of urine output. The sham operated rats receiving NS398 exhibited an increased amount of AQP-2 protein level. CONCLUSIONS:: These findings suggest that COX-2 mediated prostaglandin has an important role in the down-regulation of AQP-2 water channel level in the medullary collecting duct cells after ureteral obstruction.
This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
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X. Cheng, et al., investigated whether the decrease in AQP2 is regulated by cyclooxygenase 2 (COX-2). Ureteral obstruction increases the number of COX-2 in the collecting duct. The researchers subjected 2 groups of rats to bilateral ureteral obstruction for 24 to 48 hours. During this time, the experimental group of rats was given NS398, a substance that inhibits the presence of COX-2. The control group was not given this. The team then measured both COX-2 and AQP2 levels and the urine output of both groups of rats. The NS398 treated rats’ AQP2 level remained high (72%) and their urine output was low compared to the group not receiving the COX-2 inhibitor. Their AQP2 level was only 32% and their urine output high. The researchers' data indicate that the increase in COX-2 instigated by ureteral obstruction plays a major role in reducing the number of AQP2 in the collecting duct cells, resulting in polyuria after the obstruction is relieved.