Downregulation of renal aquaporins in response to unilateral ureteral obstruction.
The expression of aquaporin-2 (AQP2) is decreased in rats with bilateral ureteral obstruction (BUO) and unilateral ureteral obstruction (UUO). Therefore, the expression of additional renal aquaporins (AQP1-4) and phosphorylated AQP2 (p-AQP2), known to play a role in urinary concentration, was examined in a Wistar rat model with 24 h of UUO. In obstructed kidneys, immunoblotting revealed a significant decrease in the expression of inner medullary AQP2 to 42 +/- 4, p-AQP2 to 23 +/- 5, AQP3 to 19 +/- 6, AQP4 to 11 +/- 5, and AQP1 to 64 +/- 8% of sham levels. AQP1 expression located in the proximal tubule decreased to 74 +/- 4% of sham levels (P < 0.05). Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p-AQP2. In contralateral nonobstructed kidneys, immunoblotting also revealed significant reductions of AQP1 in the inner medulla, outer medulla, and cortex, whereas expression of AQP2, AQP3, AQP4, and p-AQP2 was unchanged. Furthermore, we collected the urine from both obstructed and nonobstructed kidneys for 2 h, respectively, after 24 h of UUO. Urine collection from obstructed kidneys during 2 h after release of UUO revealed a significant reduction in urine osmolality and solute-free water reabsorption (T(c)H(2)O). Moreover, an increase in urine production and T(c)H(2)O was observed in contralateral kidneys. To examine whether vasopressin-independent mechanisms are involved in AQP2 regulation, vasopressin-deficient Brattleboro (BB) rats with 24 h of UUO were examined. Immunoblotting revealed downregulation of AQP2, p-AQP2, AQP3, and AQP1 in obstructed kidneys and downregulation of p-AQP2 and AQP1 in nonobstructed kidneys. In conclusion, 1) UUO is associated with severe downregulation of AQP2, AQP3, AQP4, and AQP1; thus all of these AQPs may play important roles in the impaired urinary concentrating capacity in the obstructed kidney; 2) the reduced levels of AQP1 in the nonobstructed kidney may contribute to the compensatory increase in urine production; and 3) downregulation of AQPs in BB rats supports the view that vasopressin-independent pathways may be involved in AQP2 and AQP3 regulation in the obstructed kidney.
Li
Chunling
C
The Water and Salt Research Center, University of Aarhus, DK-8000 Aarhus C, Denmark.
Wang
Weidong
W
Knepper
Mark A
MA
Nielsen
Søren
S
Frøkiaer
Jørgen
J
D000818:Animals; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism*; D015536:Down-Regulation; D007668:Kidney / Q000378:metabolism*; D007671:Kidney Concentrating Ability; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000503:physiopathology; D014667:Vasopressins / Q000502:physiology
C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; C496032:Aqp4 protein, rat; D051399:Aquaporin 2; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D014667:Vasopressins; D051398:Aquaporin 1; D051400:Aquaporin 3