Nephrotic syndrome is often accompanied by
sodium retention and generalized
edema. We hypothesize that dysregulation of the
epithelial sodium channel (ENaC) and/or of
sodium (
co)transporters may be responsible for the increased
sodium retention associated with HgCl(2)-induced nephropathy. In addition, we examined the hypothesis that the expression of type 2
11beta-hydroxysteroid dehydrogenase (11betaHSD2) is reduced, contributing to the enhanced
mineralocorticoid activity.
Membranous nephropathy was induced in Brown Norway rats by repeated
injections of HgCl(2) (1 mg/kg sc), whereas the control group received only vehicle. After 13 days of treatment, the abundance of ENaC subunits,
sodium (
co)transporters, and 11betaHSD2 in the kidney was examined by immunoblotting and immunohistochemistry. HgCl(2) treatment induced marked
proteinuria,
hypoalbuminemia, decreased urinary
sodium excretion, and
ascites. The
protein abundance of alpha-ENaC was increased in the cortex/outer stripe of outer medulla (OSOM) and inner stripe of the outer medulla (ISOM). The
protein abundances of beta-ENaC and gamma-ENaC were decreased in the cortex/OSOM while increased in the ISOM. Immunoperoxidase microscopy demonstrated increased targeting of ENaC subunits to the apical plasma membrane in the distal convoluted tubule, connecting tubule, and cortical and medullary collecting duct segments. Moreover, 11betaHSD2 abundance was decreased in cortex/OSOM and ISOM. The
protein abundances of type 3
Na/H exchanger (NHE3), Na-K-2Cl
cotransporter (NKCC2), and
thiazide-sensitive Na-Cl cotransporter (NCC) were decreased. Moreover, the abundance of the alpha-1 subunit of the Na-K-
ATPase was decreased in the cortex/OSOM and ISOM but remained unchanged in the inner medulla. These results suggest that increased apical targeting of ENaC subunits combined with diminished abundance of 11betaHSD2 may contribute to
sodium retention associated with HgCl(2)-induced
nephrotic syndrome. The decreased abundance of NHE3, NKCC2, NCC, and Na-K-
ATPase may play a compensatory role in promoting
sodium excretion.