Interaction of ethanol, prostacyclin, and aspirin in determining human platelet reactivity in vitro.
Ethanol partitions into cellular membranes and alters membrane-associated phenomena in numerous cell types. Since platelet aggregation and its inhibition by prostacyclin are mediated by membrane-associated receptors and enzymes, we examined the interaction of ethanol, prostacyclin, and aspirin on human platelet reactivity. Using platelet-rich plasma, we examined the effect of increasing concentrations of ethanol (0.05% to 1.0%) on the platelet-inhibitory effects of a submaximal dose (5 x 10(-10) M) of prostacyclin, the concomitant production of cyclic 3',5'-adenosine monophosphate (AMP), and the release of thromboxane A2. Ethanol alone had little effect on platelet aggregation induced by 5 micrograms/ml collagen; however, it potentiated the inhibitory effect of prostacyclin on platelet aggregation in a dose-dependent manner in the range of 0.05% to 1.0% ethanol. Whereas prostacyclin increased platelet cyclic AMP levels, ethanol had no further effect on cyclic AMP levels. Ethanol alone reduced thromboxane A2 generation, but this effect could not totally account for the observed interaction of ethanol and prostacyclin on aggregation, since aspirin did not totally abolish the interaction. The dose range in which the ethanol/prostacyclin/aspirin interactions occur encompasses the plasma levels of ethanol that may be achieved by the consumption of alcoholic beverages. The results may, in part, explain the dose-related physiological and pathological consequences of chronic alcohol consumption on the cardiovascular system.
Jakubowski
J A
JA
Department of Hemostasis Research, Boston Veterans Administration Medical Center, Massachusetts 02130.
Vaillancourt
R
R
Deykin
D
D
D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D011464:Epoprostenol / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000378:metabolism
D000431:Ethanol; D013928:Thromboxane A2; D003094:Collagen; D011464:Epoprostenol; D000242:Cyclic AMP; D001241:Aspirin