title: Resveratrol Protects and Restores Endothelium-Dependent Relaxation in Hypercholesterolemic Rabbit Corpus Cavernosum.
abstract: BACKGROUND
  Oxidative stress dependent-decrease in nitric oxide (NO) bioavailability plays an integral role in hypercholesterolemia-induced erectile dysfunction (ED). Resveratrol has been demonstrated to exert beneficial effects against oxidative stress and improve NO bioavailability.
  
  
  OBJECTIVE
  The protective and restorative potentials of resveratrol on endothelium-dependent relaxations were evaluated in hypercholesterolemic rabbit corpus cavernosum (CC).
  
  
  METHODS
  Hypercholesterolemia was induced by administering 2% cholesterol diet (CD) (w/w) to the rabbits for 6 weeks. Two different protocols were applied to test the effects of resveratrol on hypercholesterolemia-induced ED. In Protocol-1 (P1), resveratrol was administrated to the rabbits simultaneously with CD in order to evaluate the protective effect, and for Protocol-2 (P2), resveratrol was administrated for 6 weeks after termination of CD in order to evaluate the restorative effect.
  
  
  METHODS
  Endothelium-dependent relaxations of CC were evaluated by using organ bath studies. In order to elucidate the possible molecular mechanisms, we measured endothelial NO synthase (eNOS) and phosphovasodilator-stimulated phosphoprotein (VASP) expressions and activations, NADPH oxidase, superoxide dismutase (SOD), and catalase (CAT) and glutathione peroxidase (GPx) activity in cavernosal tissues obtained at the end of the study.
  
  
  RESULTS
  Resveratrol showed an improvement in the endothelium-dependent relaxation responses in vitro. We demonstrated significantly increased activatory-phosphorylation (p[S1177]-eNOS) and activated phosphovasodilator-stimulated phosphoprotein (phospho-VASP) levels, but reduced phosphorylation (p[T495]-eNOS) of eNOS and NADPH oxidase activity in the resveratrol-administered HC animals compared with hypercholesterolemic control rabbits in the P1. In the P2, resveratrol exhibited an improvement in endothelium-dependent relaxation responses and more pronounced effects on eNOS activation.
  
  
  CONCLUSIONS
  Resveratrol administration, either simultaneously with HC diet or after HC, caused an improvement in the endothelium-dependent relaxation responses in the CC, suggesting its potential in both protective and restorative purposes in hypercholesterolemic rabbit CC.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey. Electronic address: nergis.murat@deu.edu.tr.
authors.forename: Nergiz
authors.initials: N
authors.lastname: Murat
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Peyda
authors.initials: P
authors.lastname: Korhan
authors.affiliation: Department of Urology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Onur
authors.initials: O
authors.lastname: Kizer
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Sinem
authors.initials: S
authors.lastname: Evcim
authors.affiliation: Department of Urology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Aykut
authors.initials: A
authors.lastname: Kefi
authors.affiliation: Department of Urology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Ömer
authors.initials: Ö
authors.lastname: Demir
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Sedef
authors.initials: S
authors.lastname: Gidener
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Neşe
authors.initials: N
authors.lastname: Atabey
authors.affiliation: Department of Urology, Faculty of Medicine, Dokuz Eylul University, Balcova, Izmir, Turkey.
authors.forename: Ahmet Adil
authors.initials: AA
authors.lastname: Esen
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D004727:Endothelium / Q000473:pathology*; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology*; D006937:Hypercholesterolemia / Q000150:complications* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010413:Penis / Q000187:drug effects / Q000473:pathology*; D011817:Rabbits; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D002791:Cholesterol, Dietary; D013267:Stilbenes; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D000077185:Resveratrol
keywords: Erectile Dysfunction; Hypercholestrolemia; Resveratrol