title: Alcohol-induced endothelial changes are associated with oxidative stress and are rapidly reversed after withdrawal.
abstract: BACKGROUND
  Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress.
  
  
  METHODS
  We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure.
  
  
  RESULTS
  Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium.
  
  
  CONCLUSIONS
  Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage.
authors.affiliation: Department of Internal Medicine and Liver Unit, Institute of Clinical Pathology, University of Udine School of Medicine, Udine, Italy. giorgio.soardo@med.uniud.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Soardo
authors.forename: Debora
authors.initials: D
authors.lastname: Donnini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Varutti
authors.forename: Massimo
authors.initials: M
authors.lastname: Moretti
authors.forename: Carla
authors.initials: C
authors.lastname: Milocco
authors.forename: Lorenza
authors.initials: L
authors.lastname: Basan
authors.forename: Walter
authors.initials: W
authors.lastname: Esposito
authors.forename: Daniele
authors.initials: D
authors.lastname: Casaccio
authors.forename: Giuliana
authors.initials: G
authors.lastname: Stel
authors.forename: Cristiana
authors.initials: C
authors.lastname: Catena
authors.forename: Francesco
authors.initials: F
authors.lastname: Curcio
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Sechi
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000473:pathology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000097:blood; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D016166:Free Radical Scavengers; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D009569:Nitric Oxide; D008315:Malondialdehyde; D005978:Glutathione