Possible Interaction: Ethanol and Epoprostenol

“Acute exposure to alcohol levels which produced moderate blood alcohol concentration (BAC) was associated with increased vascular production of prostacyclin (PGI2) and plasma catecholamines, whereas platelet production of thromboxane (TXA2) decreased.”

“ Ethanol decreased PGI2 production in a concentration-dependent manner (p < 0.05).”

“Preincubation of platelets with agents that increase levels of cAMP (i.e., forskolin, prostacyclin ) inhibited these responses to ethanol in a concentration- and time-dependent manner.”

“ Ethanol alone had little effect on platelet aggregation Induced by 5 /tg/ml collagen; however, It potentiated the Inhibitory effect of prostacyclin on platelet aggregation In a dosedependent manner in the range of 0.05% to 1.0% ethanol.”

“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.”

“However, ethanol in concentrations as low as 10 mg% potentiated the platelet aggregation inhibitory effects of prostacyclin.”

“In addition, ethanol (20 mg%) decreased formation of thromboxane A2 in whole blood by 41% and stimulated formation of prostacyclin by 160% (both P less than 0.01).”

“We, therefore, hypothesized that ethanol may influence biosynthesis and/or bioactivity of prostacyclin.”

“Landolfi and Steiner’s elegant study’ shows that ethanol increases prostacyclin (PGI2) concentration, both in vitro and in vivo.”

“Whether moderate ethanol intake exerts a more protracted effect on PGI2 and TXA2 synthesis remains speculative at present,5 but deserves further investigation.”

“Administration of 32 g of ethanol to six volunteers elevated plasma levels of PGI2 in parallel with those of blood alcohol.”

“Although not specific for ethanol, this alcohol induced the largest change in PGI2.”

“Moderate doses of ethanol were shown to induce a significant rise in prostacyclin (PGI2) concentration in cultures of endothelial cells derived from umbilical veins.”

“We propose that decreased prostacyclin production by liver non-parenchymal cells may contribute to the hepatotoxic effect of ethanol.”

“Exposure to 100% ethanol (with and without mild irritant pretreatment) significantly increased prostanoid synthesis (especially PGI2 , PGF2 alpha, and PGE2) compared with stomachs exposed to water or 25% ethanol alone; only mild irritant treated mucosa was protected from injury by 100% ethanol.”

“These ethanol effects on prostacyclin , a potent vasodilator and platelet antiaggregator, may contribute to the decreased incidence of ischemic heart disease observed in moderate alcohol drinkers.”