ADENOSINE IS A MEDIATOR OF ETHANOL-INDUCED GASTRIC VASODILATION IN DOGS

The purpose of this study was to assess the role of histamine, adenosi ne, and prostaglandins as mediators of ethanol-induced gastric vasodil ation. In an ex vivo segment of canine stomach, vasodilation occurred within the first minute of replacing luminal saline with ethanol (40% vol/vol). Ethanol caused vascular resistance to progressively decrease by approximately 53% compared with control values. In other experimen ts, intraarterial infusion of histamine (300 ng/ml) or adenosine (30 m ug/ml) to the gastric segment produced similar degrees of vasodilation as observed with ethanol. The response to these vasodilators could be markedly attenuated with specific antagonists of these substances (hi stamine: pyrilamine plus cimetidine; adenosine: 8-phenyltheophylline). In our final experiments, indomethacin or histamine- or adenosine-rec eptor antagonists were given before application of topical ethanol. In domethacin or histamine antagonists had no significant effect on the t ime course or magnitude of ethanol-induced vasodilation. In contrast, pretreatment with 8-phenyltheophylline significantly reduced changes i n vascular resistance during exposure to luminal ethanol. These result s suggest that locally released adenosine is an important mediator of ethanol-induced vasodilation in the canine stomach under these conditi ons.