Ethanol-induced increase in portal blood flow: role of adenosine.
The mechanism by which ethanol induces an increase in portal vein blood flow was studied in rats using radiolabeled microspheres. Ethanol (2 g/kg) by gavage resulted in an increase of 50-70% in portal vein blood flow. The ethanol-induced increase in portal blood flow was suppressed by the adenosine receptor blocker 8-phenyltheophylline [ethanol, 61.8 +/- 4.1 ml.kg-1.min-1; ethanol + 8-phenyltheophylline (0.2 mg.kg-1.min-1), 44.2 +/- 2.0 ml.kg-1.min-1; P less than 0.05]. By itself, 8-phenyltheophylline (0.2 mg.kg-1.min-1) was without effect on cardiac output or portal blood flow. Adenosine infusion resulted in a dose-dependent increase in portal blood flow with a maximal effect at a dose of 0.17 mg.kg-1.min-1 (control, 41.3 +/- 2.3; adenosine, 81.7 +/- 8.0 ml.kg-1.min-1; P less than 0.05). This adenosine-induced increase in portal blood flow was inhibited by 8-phenyltheophylline in a dose-dependent manner [adenosine, 81.7 +/- 8.0 ml.kg-1.min-1; adenosine + 8-phenyltheophylline (0.2 mg.kg-1.min-1), 49.8 +/- 6.6 ml.kg-1.min; P less than 0.05]. Both alcohol and adenosine significantly reduced preportal vascular resistance by 40% (P less than 0.02) and 60% (P less than 0.01), respectively. These effects were fully suppressed by 8-phenyltheophylline. It is concluded that adenosine is a likely candidate to mediate the ethanol-induced increase in portal vein blood flow. It is suggested that an increase in circulating acetate and liver hypoxia may mediate the effects of alcohol by increasing tissue and interstitial adenosine levels.
Orrego
H
H
Department of Anesthesia, Toronto Western Hospital, Ontario, Canada.
Carmichael
F J
FJ
Saldivia
V
V
Giles
H G
HG
Sandrin
S
S
Israel
Y
Y
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D011168:Portal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011983:Receptors, Purinergic / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects
D011983:Receptors, Purinergic; D000431:Ethanol; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine