Downregulation of AQP1,-2, and-3 after ureteral obstruction is associated with a long-term urine-concentrating defect

Previously, we demonstrated that 24 h of bilateral ureteral obstruction (BU O) and short-term release of BUO was associated with a decrease in the expr ession of aquaporin-2 (AQP2), polyuria, and a reduced urinary concentrating capacity (10). The purposes of the present study were to examine whether B UO and the long-term release of BUO (BUO-R) for 3, 14, and 30 days were ass ociated with changes in the expression of renal AQP1, AQP2, and AQP3 and wh ether such changes were associated with parallel changes in urinary output and urinary concentrating capacity. Rats (n = 4-7 in each group) were kept in metabolic cages for measurements of urinary output. Kidneys were removed to determine the expression levels of AQP1, AQP2, and AQP3 by semiquantita tive immunoblotting. AQP2 was downregulated after 24 h of BUO (42 +/- 3%). Downregulation of AQP2 persisted 3 (43 +/- 14%; P < 0.01) and 15 days after BUO-R (48 +/- 11%; P < 0.01) but was normalized 90 days after BUO-R. AQP3 showed a similar pattern. Moreover, AQP1 was downregulated in response to B UO (65 +/- 7%) and remained downregulated 3 days after BUO-R (41 +/- 5%), 1 4 days after BUO-R (57 +/- 8%), and 30 days after BUO-R (59 +/- 5%). BUO-R resulted in a significant polyuria that gradually decreased, although it re mained significant at day 30. Urinary concentrating capacity remained signi ficantly impaired when determined 3, 14, and 30 days after BUO-R in respons e to a 24-h period of thirst (1,712 +/- 270 vs. 2,880 +/- 91 mosmol/kgH(2)O at day 30, P < 0.05). In conclusion, the expression of AQP1, AQP2, and AQP 3 were long-term downregulated after BUO-R, suggesting that dysregulation o f aquaporins located at the proximal tubule, thin descending limb of the lo op of Henle, and the collecting duct may contribute to the long-term polyur ia and impairment of urinary concentrating capacity associated with obstruc tive nephropathy.