No abstract

1. Liver slices from rats treated with thyroxine show an increased rate of O(2) consumption. The extra consumption, but not the basal respiration, can be abolished by ouabain. 2. Dinitrophenol is not effective in increasing the rate of O(2) consumption of liver slices from thyroxine-treated animals but its effectiveness can be recovered in the presence of ouabain. 3. (Na(+)+K(+))-stimulated adenosine triphosphatase activity of liver was increased by administration of thyroxine in vivo. No changes were found in total Mg(2+)-stimulated adenosine triphosphatase activity. 4. Mitochondrial alpha-glycerophosphate dehydrogenase and microsomal NADPH oxidase activity were increased by both thyroxine and chronic ethanol treatment. 5. Liver slices from animals chronically treated with ethanol synthesize urea at an increased rate. 6. Mitochondrial size (section area) is markedly increased in the liver of animals chronically treated with ethanol. 7. Acute administration of ethanol in doses of 4 and 6g/kg significantly increases the uptake of (131)I-labelled thyroxine by the liver. 8. Work reported here, along with results from other investigators, indicates marked similarities between the effects produced in the liver by chronic administration of ethanol and by thyroid hormones.

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.

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.