Moderate ethanol (ETOH) consumption has been shown to reduce the risk of ischemic heart disease, although the mechanisms of this effect remain unclear. Recently, NO has emerged as an important endogenous inhibitor of atherogenesis. We tested the hypothesis that ETOH increases the expression of endothelial nitric oxide synthase (eNOS) and NO production in primary cultures of bovine aortic endothelial cells (BAEC). The dose-and time-dependent effects of ETOH on BAEC eNOS expression were examined by Northern and Western blotting. In separate experiments, cells were grown on microcarrier beads and NO production was quantitated by a chemiluminescence method. ETOH elicited an increase in eNOS message that occurred rapidly, peaking within 3 hr (120% increase over control values) and was still pronounced after 24 hr. This increase was confirmed at the protein level by immunoblotting. When compared to control cells, ETOH (0.1%) treatment resulted in a significant 54% increase in NO production in both basal and A23187 calcium ionophore-stimulated NO production when cells were incubated with indomethacin (p<0.05). Without cyclooxygenase inhibition, ETOH failed to increase NO production, suggesting complex reciprocal regulatory mechanisms involving NO and prostanoids. The results indicate that low concentrations of ETOH increase endothelium-derived NO production and that this increase is associated with the upregulation of eNOS mRNA and increased eNOS enzyme activity.
|Original language||English (US)|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology