Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction.
The roles of epithelial sodium channel (ENaC) subunits (alpha, beta, and gamma) in the impaired renal reabsorption of sodium and water were examined in rat models with bilateral (BUO) or unilateral ureteral obstruction (UUO) for 24 h or with BUO followed by release of obstruction and 3 days of observation (BUO-3dR). In BUO rats, plasma osmolality was increased dramatically, whereas plasma sodium concentration was decreased. Immunoblotting revealed a significantly decreased expression of alpha-ENaC (57 +/- 7%), beta-ENaC (19 +/- 5%), and gamma-ENaC (51 +/- 10%) as well as 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) in the cortex and outer medulla (C+OM) compared with sham-operated controls. This was confirmed by immunohistochemistry. BUO-3dR was associated with polyuria and impaired renal sodium handling. The protein abundance and the apical labeling of alpha-ENaC were significantly increased, whereas beta- and gamma-ENaC as well as 11beta-HSD2 expression remained decreased. In UUO rats, expression of alpha- and beta-ENaC and 11beta-HSD2 decreased in the C+OM in the obstructed kidney. In contrast, the abundance and the apical labeling of alpha-ENaC in the nonobstructed kidneys were markedly increased, suggesting compensatory upregulation in this kidney. In conclusion, alpha-, beta-, and gamma-ENaC expression levels are downregulated in the obstructed kidney. The expression and apical labeling of alpha-ENaC were increased in BUO-3dR rats and in the nonobstructed kidneys from UUO rats. These results suggest that altered expression of alpha-, beta-, and gamma-ENaC may contribute to impaired renal sodium and water handling in response to ureteral obstruction.
Li
Chunling
C
The Water and Salt Research Center, University of Aarhus, DK-8230 Aarhus N, Denmark.
Wang
Weidong
W
Norregaard
Rikke
R
Knepper
Mark A
MA
Nielsen
Søren
S
Frøkiaer
Jørgen
J
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D053503:Epithelial Sodium Channels / Q000096:biosynthesis*; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism*; D014867:Water / Q000378:metabolism
D000199:Actins; D053503:Epithelial Sodium Channels; D014867:Water; D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2