title: Proanthocyanidins from Vitis vinifera inhibit oxidative stress-induced vascular impairment in pulmonary arteries from diabetic rats.
abstract: BACKGROUND
  Vitis vinifera L. (grape seed extract) is a natural source of proanthocyanidins with antioxidant and free radical-scavenging activities.
  
  
  OBJECTIVE
  Grape seed extract supplementation may prevent vascular endothelium impairment associated with diabetes mellitus in rat pulmonary artery.
  
  
  METHODS
  We evaluated endothelial function of rat pulmonary artery ex-vivo at the intermediate stage (4 weeks) of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated the protective effect of grape seed extract administered daily, beginning the day after diabetes induction, or 15 days after diabetes induction, until the day of sacrifice. In addition, we compared the effect of grape seed extract supplementation with that of vitamin C.
  
  
  METHODS
  Rats were made diabetic with streptozotocin (STZ, 65mg/kg i.v.). Thirty days later rats were sacrificed and pulmonary vessels reactivity and endothelial function compared to that of age-matched healthy animals.
  
  
  RESULTS
  Concentration-response curves to ACh, NE, sodium nitroprusside (NO donor), but not to histamine and iloprost (prostacyclin analog), were significantly altered 4 weeks after STZ-injection. Antioxidant supplementation (3mg/kg/day) with either vitamin C or grape seed extract, starting the day after diabetes induction, significantly improved vasodilation to ACh and SNP. Norepinephrine-induced contractions were preserved by grape seed extract, but not vitamin C supplementation. Conversely, vitamin C but not grape seed extract showed beneficial effects contrasting the loss of body weight in diabetic animals. Abnormal vascular function was not reversed when antioxidant supplementations were postponed 15 days after the induction of diabetes.
  
  
  CONCLUSIONS
  This study provides scientific support for the therapeutic potential of an antioxidant therapy in endothelial impairment associated with diabetes. A daily supplementation of grape seed proanthocyanidins and/or vitamin C given at the earlier stage of disease may have a complementary role in the pharmacological therapy of diabetes and pulmonary vascular dysfunction.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti, 9, 20133 Milanο, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Pinna
authors.affiliation: Indena S.p.A. R&D, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Morazzoni
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan, via Balzaretti, 9, 20133 Milanο, Italy; IBIM, National Research Council, Via Ugo la Malfa 153, 90146 Palermo, Italy. Electronic address: angelo.sala@unimi.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sala
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000494:pharmacology; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D056604:Grape Seed Extract / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D044945:Proanthocyanidins / Q000494:pharmacology* / Q000627:therapeutic use; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects; D027843:Vitis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D020030:Nitric Oxide Donors; D044945:Proanthocyanidins; D009599:Nitroprusside; D001205:Ascorbic Acid
keywords: Antioxidant treatment; Diabetes; Oxidative stress; Proanthocyanidins; Pulmonary vascular impairment