Eplerenone suppresses salt-induced vascular endothelial growth factor expression in the kidney.
OBJECTIVE
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.
Eatman
Danita
D
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Ga., USA.
Layas
Mohammed F
MF
Bayorh
Mohamed A
MA
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D000077545:Eplerenone; D005786:Gene Expression Regulation; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D051381:Rats; D020303:Rats, Inbred Dahl; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D000451:Mineralocorticoid Receptor Antagonists; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D013148:Spironolactone; D000077545:Eplerenone