Cyclooxygenase-2 Inhibitor Preserves Medullary Aquaporin-2 Expression and Prevents Polyuria After Ureteral Obstruction

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.