In vitro and in vivo effects of ethanol on the formation of endoperoxide metabolites in rat platelets.

Preincubation of rat platelet-rich plasma (PRP) with ethanol resulted in dose-dependent inhibition of the formation of endoperoxide metabolites (EPM) when the PRP was aggregated by collagen suspension. The inhibition was manifested at concentrations normally attainable in blood of rats or humans by tolerable amounts of ethanol ingestion. Paradoxically, chronic ingestion of ethanol caused enhanced synthesis of EPM in platelets, indicating that the inhibitory effect of ethanol would be temporary, and that it can be reversed as soon as ethanol is eliminated. The level of arachidonic acid in platelet phospholipids of rats fed the ethanol diet was not different from that of the control, indicating that availability of immediate precursor acid would not be a factor for the enhanced synthesis of EPM in the ethanol group. This result suggested that platelets from rats subjected to chronic ethanol ingestion become hyperactive in synthesizing EPM through an unknown mechanism. When citrated whole blood was incubated in the presence of collagen suspension, amounts of EPM synthesized in the ethanol group were not different from those of the control group, but this was due to significant reduction of platelet counts in the ethanol group. Whether the effect of ethanol on other tissues would be similar to that on platelets is unknown. It is tempting to speculate that some of the pathological changes resulting from alcoholism might be mediated through the effect of ethanol on EPM formation.