Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin

Eur J Nutr. 2016 Mar;55(2):749-758. doi: 10.1007/s00394-015-0895-0. Epub 2015 Apr 11.


Purpose: The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS).

Methods: Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration.

Results: GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by L-NAME and partially inhibited by indomethacin.

Conclusions: GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.

Keywords: Antihypertensive agent; Cafeteria diet; Endothelial-relaxing factors; Hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects*
  • Diet / adverse effects
  • Dose-Response Relationship, Drug
  • Epoprostenol / antagonists & inhibitors
  • Epoprostenol / metabolism*
  • Grape Seed Extract / pharmacology*
  • Hypertension / chemically induced
  • Hypertension / drug therapy
  • Indomethacin / pharmacology
  • Male
  • Metabolic Syndrome / drug therapy*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Polyphenols / pharmacology*
  • Rats
  • Rats, Wistar
  • Seeds / chemistry
  • Vitis / chemistry


  • Antihypertensive Agents
  • Grape Seed Extract
  • Polyphenols
  • Nitric Oxide
  • Epoprostenol
  • NG-Nitroarginine Methyl Ester
  • Indomethacin