title: 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.
abstract: OBJECTIVE
  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.
authors: Nutrigenomic Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, C/Marcel.lí Domingo, 43007, Tarragona, Spain.
authors: Zara
authors: Z
authors: Pons
authors: Nutrigenomic Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, C/Marcel.lí Domingo, 43007, Tarragona, Spain.
authors: Maria
authors: M
authors: Margalef
authors: Nutrigenomic Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, C/Marcel.lí Domingo, 43007, Tarragona, Spain.
authors: Francisca I
authors: FI
authors: Bravo
authors: Nutrigenomic Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, C/Marcel.lí Domingo, 43007, Tarragona, Spain. anna.arola@urv.cat.
authors: Anna
authors: A
authors: Arola-Arnal
authors: Nutrigenomic Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, C/Marcel.lí Domingo, 43007, Tarragona, Spain.|Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Tarragona, Spain.
authors: Begoña
authors: B
authors: Muguerza
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004032:Diet / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056604:Grape Seed Extract / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D059808:Polyphenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D027843:Vitis / Q000737:chemistry
chemical_list: D000959:Antihypertensive Agents; D056604:Grape Seed Extract; D059808:Polyphenols; D009569:Nitric Oxide; D011464:Epoprostenol; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin
keywords: Antihypertensive agent; Cafeteria diet; Endothelial-relaxing factors; Hypertension