Vanillic acid prevents the deregulation of lipid metabolism, endothelin 1 and up regulation of endothelial nitric oxide synthase in nitric oxide deficient hypertensive rats

Eur J Pharmacol. 2014 Nov 15;743:117-25. doi: 10.1016/j.ejphar.2014.09.010. Epub 2014 Sep 17.


Hypertension is one of the main factors causing cardiovascular diseases. The present study was designed to evaluate the protective effect of vanillic acid against nitric oxide deficient rats. Hypertension was induced in adult male albino rats of Wistar strain, weighing 180-220g, by oral administration of N(ω)-nitro-l arginine methyl ester (l-NAME) 40mg/kg in drinking water for 4 weeks. Vanillic acid was administered orally at a dose of 50mg/kg b.w. Nitric oxide deficient rats showed increased levels of mean arterial pressure (MAP), heart rate (HR) and decreased heart nitric oxide metabolites (NOx). A significant increase in the levels of plasma cholesterol, low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C), triglycerides (TG), free fatty acids (FFA), phospholipids (PL), 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase in the plasma, liver and kidney and decreased level of high density lipoprotein-cholesterol (HDL-C) are observed, whereas there is a decrease in the activities of plasma lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) in nitric oxide deficient rats. l-NAME rats also showed an increase in TC, TG, FFA and PL levels in the liver and kidney tissues. Vanillic acid treatment brought the above parameters towards near normal level. Moreover the down regulated endothelial nitric oxide synthase (eNOS) and up regulated expression of endothelin 1 (ET1) components was also attenuated by vanillic acid treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that vanillic acid has enough potential to attenuate hypertension, dyslipidemia and hepatic and renal damage in nitric oxide deficient rats.

Keywords: Dyslipidemia; Endothelial nitric oxide synthase; Endothelin; Vanillic acid; l-NAME.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / drug effects
  • Endothelin-1 / metabolism*
  • Heart / drug effects
  • Heart Rate / drug effects
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Lipid Metabolism / drug effects*
  • Lipids / blood
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / metabolism*
  • Rats
  • Rats, Wistar
  • Up-Regulation / drug effects*
  • Vanillic Acid / pharmacology*


  • Endothelin-1
  • Lipids
  • Nitric Oxide
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Vanillic Acid