Eplerenone suppresses salt-induced vascular endothelial growth factor expression in the kidney

Abstract

Background/aim: It is well accepted that high dietary salt intake accelerates both hypertension and target organ damage. We have previously shown that eplerenone attenuates sustained elevated systolic blood pressure in Dahl salt-sensitive (SS) rats. In the present study, we investigated the role of eplerenone on vascular endothelial growth factor (VEGF) expression because we suspected that eplerenone treatment may trigger a unique mechanism that relies on the downregulation of VEGF.

Methods: Dahl SS rats were fed a high salt (8% NaCl) diet for 3 weeks and then switched to normal salt (0.3% NaCl) diet with or without treatment with eplerenone (100 mg/kg/day), enalapril (30 mg/kg/day) and their combination for an additional 3 weeks.

Results: In addition to reducing blood pressure, eplerenone inhibited glomeruli sclerosis and suppressed the expression of VEGF and endothelial nitric oxide synthase mRNA as well as protein levels.

Conclusions: Based on these findings, we suggest that in part, VEGF stimulation of endothelial nitric oxide synthase plays a significant role in the eplerenone-induced reversal of the renal and vascular damage caused by high dietary salt intake.

Fig. 1

Glomeruli sclerosis in Dahl SS rats. Photomicrographs (orig. magnif. × 200) of the histopathology of HE-stained kidney sections from SS rats fed 3 weeks high salt diet followed by 3 weeks low salt diet (control) with or without drug treatment with enalapril treatment (ENA), eplerenone (EPL), or their combination (ENA + EPL). Sections shown are typical of the 4 rats/group. a Control sections showing severe focal glomerulosclerosis (arrow highlights glomerulosclerosis). b Kidney section from an ENA-treated rat showing mild focal glomerulosclerosis. c Section from an EPL-treated rat showing no histopathologic changes.

Fig. 2

Renal VEGF and eNOS protein expression in Dahl SS rats fed a low or high salt diet with eplerenone (100 mg/kg/day). Representative Western blot of a VEGF, b eNOS, and c relative VEGF and eNOS content (arbitrary units). Densitometry units were normalized to actin. Data represent the mean ± SEM of three replicates. ∗ p < 0.05 when compared to LS; ∗∗ p < 0.05 when compared to LS/EPL; # p < 0.05 when compared to HS.