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.