Altered expression of epithelial sodium channel in rats with bilateral or unilateral ureteral obstruction

Abstract

.-The roles of epithelial sodium channel (ENaC) subunits (␣, ␤, and ␥) 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 ␣-ENaC (57 Ϯ 7%), ␤-ENaC (19 Ϯ 5%), and ␥-ENaC (51 Ϯ 10%) as well as 11␤-hydroxysteroid dehydrogenase type 2 (11␤-HSD2) in the cortex and outer medulla (CϩOM) 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 ␣-ENaC were significantly increased, whereas ␤-and ␥-ENaC as well as 11␤-HSD2 expression remained decreased. In UUO rats, expression of ␣-and ␤-ENaC and 11␤-HSD2 decreased in the CϩOM in the obstructed kidney. In contrast, the abundance and the apical labeling of ␣-ENaC in the nonobstructed kidneys were markedly increased, suggesting compensatory upregulation in this kidney. In conclusion, ␣-, ␤-, and ␥-ENaC expression levels are downregulated in the obstructed kidney. The expression and apical labeling of ␣-ENaC were increased in BUO-3dR rats and in the nonobstructed kidneys from UUO rats. These results suggest that altered expression of ␣-, ␤-, and ␥-ENaC may contribute to impaired renal sodium and water handling in response to ureteral obstruction.

The Inhibitory Effect of Eplerenone on Cell Proliferation in the Contralateral Kidneys of Rats with Unilateral Ureteral Obstruction

“…The animal study showed that levels of aldosterone in Munich Wister rats increased after 24 h of UUO compared with the sham rats (404 ± 41 vs. 208 ± 30 pg/mL), and increased significantly in bilateral ureteral obstruction rats (3,610 ± 246 pg/mL). These results suggest that plasma aldosterone concentration is closely related to ureteral ligation [24] . It has been discussed that the intrarenal reninangiotensin system is activated in the obstructed kidney of UUO [25] .…”

Effects of amiloride, benzamil, and alterations in extracellular Na+ on the rat afferent arteriole and its myogenic response

“…Despite these similarities, it was suggested that the mechanisms underlying the myogenic response in the hydronephrotic kidney model might differ from those of the normal kidney, since it was recently reported by Li et al (22) that ENaC expression in the CCD is rapidly downregulated following ureteral obstruction. This same group (12) had previously surveyed ENaC expression in the rat kidney.…”

Diabetes Insipidus: A Review

“…These defects, combined with decreased urinary concentrating capability, increased ANP, and the supernormal volume of fluid and solute, leads to dieresis [95]. In patients with significant obstruction, this impaired concentrating capability may remain long after the obstruction is removed [94][95][96][97]. It is postulated that defects in AQP1 expression are the cause of continued urinary obstruction-associated polyuria [94].…”