Nephrotic syndrome (NS) is a clinical state characterized by massive
proteinuria and
edema. It is believed that
nephrin and
podocin are involved in the development of
proteinuria. The
proteinuria and effects of
eplerenone alone or combined with
enalapril on
nephrin/
podocin abundance in rats with NS have not yet been studied. Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 wk after NS induction) effects of
eplerenone and
enalapril, alone or combined, on
proteinuria and
nephrin/
podocin abundance in rats with
adriamycin-induced NS.
Adriamycin caused a significant increase in daily
protein excretion (U(pr)V; from 26.96 +/- 3.43 to 958.57 +/- 56.7 mg/day, P < 0.001) and cumulative
proteinuria [from 900.33 +/- 135.5 to 22,490.62 +/- 931.26 mg (P < 0.001)] during 6 wk. Early treatment with
enalapril significantly decreased U(pr)V from 958.6 +/- 56.7 to 600.31 +/- 65.13 mg/day (P < 0.001) and cumulative
proteinuria to 12,842.37 +/- 1,798.17 mg/6 wk (P < 0.001). Similarly, early treatment with
eplerenone produced a profound antiproteinuric effect: U(pr)V decreased from 958.57 +/- 56.7 to 593.38 +/- 21.83 mg/day, P < 0.001, and cumulative
proteinuria to 16,601.84 +/- 1,334.31 mg/6 wk; P < 0.001. An additive effect was obtained when
enalapril and
eplerenone were combined: U(pr)V decreased from 958.57 +/- 56.69 to 424.17 +/- 38.54 mg/day, P < 0.001, and cumulative
protein excretion declined to 10,252.88 +/- 1,011.3 mg/6 wk, P < 0.001. These antiproteinuric effects were associated with substantial preservation of glomerular
nephrin and
podocin. In contrast, late treatment with either
enalapril or
eplerenone alone or combined mildly decreased U(pr)V and cumulative
proteinuria. Thus pretreatment with
eplerenone or
enalapril is effective in reducing daily and cumulative
protein excretion and preservation of
nephrin/
podocin. More profound antiproteinuric effects were obtained when
enalapril and
eplerenone were combined.