Adenosine is a mediator of ethanol-induced gastric vasodilation in dogs

The purpose of this study was to assess the role of histamine, adenosine, and prostaglandins as mediators of ethanol-induced gastric vasodilation. 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 experiments, intra-arterial infusion of histamine (300 ng/ml) or adenosine (30 micrograms/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 (histamine: pyrilamine plus cimetidine; adenosine: 8-phenyltheophylline). In our final experiments, indomethacin or histamine- or adenosine-receptor antagonists were given before application of topical ethanol. Indomethacin or histamine antagonists had no significant effect on the time course or magnitude of ethanol-induced vasodilation. In contrast, pretreatment with 8-phenyltheophylline significantly reduced changes in vascular resistance during exposure to luminal ethanol. These results suggest that locally released adenosine is an important mediator of ethanol-induced vasodilation in the canine stomach under these conditions.