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 (BUO) and short-term release of BUO was associated with a decrease in the expression of aquaporin-2 (AQP2), polyuria, and a reduced urinary concentrating capacity (10). The purposes of the present study were to examine whether BUO and the long-term release of BUO (BUO-R) for 3, 14, and 30 days were associated with changes in the expression of renal AQP1, AQP2, and AQP3 and whether 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 semiquantitative 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 30 days after BUO-R. AQP3 showed a similar pattern. Moreover, AQP1 was downregulated in response to BUO (65 +/- 7%) and remained downregulated 3 days after BUO-R (41 +/- 5%), 14 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 remained significant at day 30. Urinary concentrating capacity remained significantly impaired when determined 3, 14, and 30 days after BUO-R in response to a 24-h period of thirst (1,712 +/- 270 vs. 2,880 +/- 91 mosmol/kgH2O at day 30, P < 0.05). In conclusion, the expression of AQP1, AQP2, and AQP3 were long-term downregulated after BUO-R, suggesting that dysregulation of aquaporins located at the proximal tubule, thin descending limb of the loop of Henle, and the collecting duct may contribute to the long-term polyuria and impairment of urinary concentrating capacity associated with obstructive nephropathy.
Li
C
C
Institute of Experimental Clinical Research, University of Aarhus, DK-8200 Aarhus N, Denmark.
Wang
W
W
Kwon
T H
TH
Isikay
L
L
Wen
J G
JG
Marples
D
D
Djurhuus
J C
JC
Stockwell
A
A
Knepper
M A
MA
Nielsen
S
S
Frøkiaer
J
J
D000818:Animals; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051403:Aquaporin 6; D020346:Aquaporins / Q000032:analysis / Q000378:metabolism*; D002458:Cell Fractionation; D015536:Down-Regulation; D015151:Immunoblotting; D007671:Kidney Concentrating Ability; D007685:Kidney Tubules, Collecting / Q000503:physiopathology; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D009399:Nephrons / Q000503:physiopathology*; D009994:Osmolar Concentration; D011141:Polyuria / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014517:Ureteral Obstruction / Q000503:physiopathology* / Q000652:urine
C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D051398:Aquaporin 1; D051400:Aquaporin 3