ETHANOL POTENTIATES INTERLEUKIN-1-BETA-STIMULATED INDUCIBLE NITRIC-OXIDE SYNTHASE EXPRESSION IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS

Experiments were performed to examine the effect of ethanol on the pro duction of nitric oxide from interleukin-1 beta (IL-1 beta)-treated cu ltured rat aortic smooth muscle cells, Incubation of vascular smooth m uscle cells with IL-1 beta resulted in the release of nitrite and in t he intracellular accumulation of L-citrulline, In parallel with this, IL-1 beta increased inducible nitric oxide synthase (iNOS) mRNA and pr otein, Ethanol (6.5-650 mM) potentiated the IL-1 beta-mediated stimula tion of iNOS mRNA production, the appearance of iNOS protein and the g eneration of nitrite and L-citrulline from smooth muscle cells in a co ncentration-dependent manner. In the absence of IL-1 beta, ethanol fai led to induce iNOS expression, These results demonstrate that pharmaco logically relevant concentrations of ethanol enhance the IL-1 beta-ind uced expression of the iNOS gene in vascular smooth muscle. The abilit y of ethanol to augment the release of the platelet inhibitor and vaso dilator nitric oxide may, in part, contribute to the beneficial cardio vascular effects associated with moderate alcohol consumption.