Ethanol-induced increase in portal blood flow: role of acetate and A1- and A2-adenosine receptors.
The increase in portal blood flow induced by ethanol appears to be adenosine mediated. Acetate, which is released by the liver during ethanol metabolism, is known to increase adenosine levels in tissues and in blood. The effects of acetate on portal blood flow were investigated in rats using the microsphere technique. The intravenous infusion of acetate (7-250 mumol.kg-1.min-1) resulted in vasodilation of the preportal vasculature and in a dose-dependent increase in portal blood flow [control, 39.1 +/- 2.6 ml.kg-1.min-1; acetate (250 mumol.kg-1. min-1), 68.7 +/- 4.0 ml.kg-1.min-1]. This acetate-induced increase in portal blood flow was suppressed by the adenosine receptor blocker, 8-phenyltheophylline. Using the A1-adenosine receptor agonist N-6-cyclohexyl adenosine and the A2-agonist 5'-N-ethylcarboxamido adenosine, we demonstrate that the effect of adenosine on the preportal vasculature is mediated by the A2-subtype of adenosine receptors. In conclusion, these data support the hypothesis that the increase in portal blood flow after ethanol administration results from a preportal vasodilatory effect of adenosine formed from acetate metabolism in extrahepatic tissues.
Carmichael
F J
FJ
Addiction Research Foundation Clinical Institute, Toronto, Ontario, Canada.
Saldivia
V
V
Varghese
G A
GA
Israel
Y
Y
Orrego
H
H
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D004064:Digestive System / Q000098:blood supply; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008863:Microspheres; D011168:Portal System / Q000187:drug effects*; D011773:Pyruvates / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D000085:Acetates; D011773:Pyruvates; D011983:Receptors, Purinergic; D000431:Ethanol; D013806:Theophylline; C028322:8-phenyltheophylline