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

Kidney Blood Press Res. 2010;33(3):167-73. doi: 10.1159/000316700. Epub 2010 Jun 23.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Eplerenone
  • Gene Expression Regulation
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Mineralocorticoid Receptor Antagonists / pharmacology*
  • Rats
  • Rats, Inbred Dahl
  • Spironolactone / analogs & derivatives*
  • Spironolactone / pharmacology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Mineralocorticoid Receptor Antagonists
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Spironolactone
  • Eplerenone