New insights on the mechanism of the alcohol-induced increase in portal blood flow.
Acute administration of ethanol increases portal blood flow by 40-60%. This increase in blood flow compensates for the increase in O2 consumption that follows alcohol intake and may play a protective role against hypoxic hepatocellular necrosis. We have investigated the mechanism of this hemodynamic effect of ethanol in the rat using the labeled microsphere technique. We ruled out a direct role of systemic glucagon and of acetaldehyde in mediating the increase in portal flow. However, the increase in flow is maximal at a blood ethanol concentration of 3.5 mM, corresponding to that required to achieve the Vmax of alcohol dehydrogenase, and is suppressed by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. Alcohol ingestion results in zonal liver hypoxia and in increases in acetate, both of which have been shown to increase the levels of adenosine, a potent vasodilator, in blood and tissues. Ethanol produces a 400% increase in arterial adenosine. Adenosine infusion leads to a dose-dependent increase in portal blood flow of up to 100%, an effect that is suppressed by administration of 8-phenyltheophylline, an antagonist of adenosine at A1 and A2 receptors. Similarly, the ethanol-induced increase in portal blood flow is fully suppressed by 8-phenyltheophylline. In conclusion, adenosine appears to play an important role in the mechanism by which ethanol increases portal blood flow.
Orrego
H
H
Addiction Research Foundation Clinical Institute, Toronto, Ont., Canada.
Carmichael
F J
FJ
Israel
Y
Y
D000241:Adenosine / Q000097:blood; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D004285:Dogs; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats
D000431:Ethanol; D000241:Adenosine