title: Resveratrol Improved Flow-Mediated Outward Arterial Remodeling in Ovariectomized Rats with Hypertrophic Effect at High Dose.
abstract: OBJECTIVE
  Chronic increases in blood flow in resistance arteries induce outward remodeling associated with increased wall thickness and endothelium-mediated dilatation. This remodeling is essential for collateral arteries growth following occlusion of a large artery. As estrogens have a major role in this remodeling, we hypothesized that resveratrol, described as possessing phytoestrogen properties, could improve remodeling in ovariectomized rats.
  
  
  METHODS
  Blood flow was increased in vivo in mesenteric arteries after ligation of adjacent arteries in 3-month old ovariectomized rats treated with resveratrol (5 or 37.5 mg/kg per day: RESV5 or RESV37.5) or vehicle. After 2 weeks arterial structure and function were measured in vitro in high flow (HF) and normal flow (NF) arteries isolated from each rat.
  
  
  RESULTS
  Arterial diameter was greater in HF than in NF arteries in ovariectomized rats treated with RESV5 or RESV37.5, not in vehicle-treated rats. In mice lacking estrogen receptor alpha diameter was equivalent in HF and NF arteries whereas in mice treated with RESV5 diameter was greater in HF than in NF vessels. A compensatory increase in wall thickness and a greater phenylephrine-mediated contraction were observed in HF arteries. This was more pronounced in HF arteries from RESV37.5-treated rats. ERK1/2 phosphorylation, involved in hypertrophy and contraction, were higher in RESV37.5-treated rats than in RESV5- and vehicle-treated rats. Endothelium-dependent relaxation was greater in HF than in NF arteries in RESV5-treated rats only. In HF arteries from RESV37.5-treated rats relaxation was increased by superoxide reduction and markers of oxidative stress (p67phox, GP91phox) were higher than in the 2 other groups.
  
  
  CONCLUSIONS
  Resveratrol improved flow-mediated outward remodeling in ovariectomized rats thus providing a potential therapeutic tool in menopause-associated ischemic disorders. This effect seems independent of the estrogen receptor alpha. Nevertheless, caution should be taken with high doses inducing excessive contractility and hypertrophy in association with oxidative stress in HF arteries.
authors.affiliation: University of Angers, Angers, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Petit
authors.affiliation: CNRS UMR-6214, Angers, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Guihot
authors.affiliation: University of Angers, Angers, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Grimaud
authors.affiliation: University of Angers, Angers, France.|CARFI (Cardiovascular Function In vitro) facility, Angers, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Vessieres
authors.affiliation: University of Angers, Angers, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Toutain
authors.affiliation: UMR-S1144, Faculty of Pharmacy, Paris Descartes University, Paris, France, and Assistance Publique Hôpitaux de Paris, Department of Biochemistry, Cochin Hospital, Paris, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Menet
authors.affiliation: UMR-S1140, Faculty of Pharmacy, Paris Descartes University, Paris, France, and Assistance Publique Hôpitaux de Paris, Department of Biochemistry, Georges Pompidou European Hospital, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Nivet-Antoine
authors.affiliation: INSERM U1048, Toulouse III Paul Sabatier University, University hospital of Toulouse, Toulouse, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Arnal
authors.affiliation: University of Angers, Angers, France.|CNRS UMR-6214, Angers, France.|INSERM UMRS-1083, Angers, France.|UMR-S1144, Faculty of Pharmacy, Paris Descartes University, Paris, France, and Assistance Publique Hôpitaux de Paris, Department of Biochemistry, Cochin Hospital, Paris, France.|University hospital (CHU) of Angers, Angers, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Loufrani
authors.affiliation: University of Angers, Angers, France.|CNRS UMR-6214, Angers, France.|INSERM UMRS-1083, Angers, France.|University hospital (CHU) of Angers, Angers, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Procaccio
authors.affiliation: University of Angers, Angers, France.|CNRS UMR-6214, Angers, France.|INSERM UMRS-1083, Angers, France.|CARFI (Cardiovascular Function In vitro) facility, Angers, France.|University hospital (CHU) of Angers, Angers, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Henrion
mesh_terms: D000818:Animals; D064752:Atrial Remodeling / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D008562:Membrane Glycoproteins / Q000378:metabolism; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000032:analysis / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D014665:Vasodilator Agents / Q000032:analysis / Q000494:pharmacology*
chemical_list: D008562:Membrane Glycoproteins; D013267:Stilbenes; D014665:Vasodilator Agents; D013481:Superoxides; D010656:Phenylephrine; D052250:Nitric Oxide Synthase Type III; D009247:NADH, NADPH Oxidoreductases; C583073:NCF2 protein, rat; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000077185:Resveratrol