Ethanol increases endothelial nitric oxide production through modulation of nitric oxide synthase expression

Moderate alcohol consumption has been shown to reduce the risk of ischemic heart disease potentially through its effect on specific endothelial-derive d compounds. We tested the hypothesis that ethanol increases the expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) producti on in bovine aortic endothelial cells (BAEC). Primary cultures of BAEC grow n to confluence under standard conditions were treated 3-6 h with 0.1% etha nol in the presence of indomethacin. Ethanol induced a significant increase in both basal and stimulated NO production as determined by chemiluminesce nce method. This effect was accompanied by a rapid increase of eNOS protein and mRNA expression levels. eNOS mRNA increased two-fold within 3 h and gr adually declined, but the increased levels of mRNA persisted for >24 h. A s imilar increase of eNOS expression was observed in human umbilical endothel ial cells exposed to ethanol, These results demonstrate that ethanol augmen ts both basal acid stimulated NO production and that this effect is associa ted with increased eNOS protein and mRNA expression levels, The data are co nsistent with the hypothesis that the reduced incidence of ischemic heart d isease associated with alcohol may be related, at least in part, to the mod ulation of vascular endothelial cell production of NO.