Alcohol-induced endothelial changes are associated with oxidative stress and are rapidly reversed after withdrawal.
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.
Soardo
Giorgio
G
Department of Internal Medicine and Liver Unit, Institute of Clinical Pathology, University of Udine School of Medicine, Udine, Italy. giorgio.soardo@med.uniud.it
Donnini
Debora
D
Varutti
Rosanna
R
Moretti
Massimo
M
Milocco
Carla
C
Basan
Lorenza
L
Esposito
Walter
W
Casaccio
Daniele
D
Stel
Giuliana
G
Catena
Cristiana
C
Curcio
Francesco
F
Sechi
Leonardo A
LA
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
D019332:Endothelin-1; D016166:Free Radical Scavengers; D017395:Plasminogen Activator Inhibitor 1; D014841:von Willebrand Factor; D009569:Nitric Oxide; D008315:Malondialdehyde; D005978:Glutathione