Adenosine A2-receptor mediates ethanol-induced arteriolar dilation in rat stomach.

Topical application of ethanol to the gastrointestinal mucosa induces vasodilation. Using an in vivo microscopy technique, we studied the effect of topical ethanol on the submucosal microvessels that control mucosal blood flow in the rat stomach and identified vasoactive substances and receptors that mediate the ethanol vasoaction. Topical ethanol (1-20%) dilated submucosal arterioles dose dependently, but did not change venular diameters. An inhibitor of alcohol dehydrogenase, 1 mM 4-methylpyrazole, did not alter the ethanol vasoaction. Ethanol-induced arteriolar dilation was eliminated by adenosine deaminase, but other vasodilator inhibitors such as atropine, pyrilamine, indomethacin, human calcitonin gene-related peptide-(8-37), and N omega-nitro-L-arginine methyl ester did not prevent it. Ethanol-induced arteriolar dilation was inhibited by an adenosine A2-receptor antagonist, but not by an A1-receptor antagonist, whereas an A2-agonist, but not an A1-agonist, dose dependently dilated arterioles. Exogenous adenosine (10(-5)-10(-3) M) dilated arterioles to a similar extent as ethanol. This response was inhibited by an A2-antagonist. We conclude that nonmetabolized ethanol increases gastric mucosal blood flow via A2-receptors in submucosal arterioles.