Increased renal ENaC subunits and sodium retention in rats with chronic heart failure.

ABSTRACT: Renal tubular dysfunction could be involved in the increased sodium and water reabsorption in chronic heart failure (CHF). The goal of the present study was to examine the molecular basis for the increased renal sodium and water retention in CHF. We hypothesized that dysregulation of renal epithelial sodium channels (ENaC) could be involved in the pathogenesis of CHF. The left coronary ligation-induced model of heart failure in the rat was used. Real-time PCR and Western blot analysis indicated that the mRNA and protein abundance of ?-, ?-, and ?-subunits of ENaC were significantly increased by in the cortex (mRNA: ?-ENaC ?104 ± 24%, ?-ENaC ?47 ± 16%, ?-ENaC ?55 ± 18%; protein: ?-ENaC ?114 ± 28%, ?-ENaC ?150 ± 31%, ?-ENaC ?39 ± 5% compared with sham rats) and outer medulla (mRNA: ?-ENaC ?52 ± 18%, ?-ENaC ?38 ± 8%, ?-ENaC ?39 ± 13%; protein: ?-ENaC ?88 ± 16%, ?-ENaC ?94 ± 28%, ?-ENaC ?45 ± 9% compared with sham rats) of CHF compared with sham-operated rats. Immunohistochemistry microscopy confirmed the increased labeling of ?-, ?-, and ?-ENaC subunits in the collecting duct segments in rats with CHF. Furthermore, there was a significant increase in diuretic (7-fold compared with sham) and natriuretic responses (3-fold compared with sham) to ENaC inhibitor benzamil in the rats with CHF. Absence of renal nerves produced a greater contribution of ENaC in sodium retention in rats with CHF. These results suggest that the increased expression of renal ENaC subunits may contribute to the renal sodium and water retention observed during CHF.

SUBMITTER: Zheng H 

PROVIDER: S-EPMC4068120 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature