Hormonal influences in the development of the hypermetabolic state of the liver produced by chronic administration of ethanol.

Chronic administration of ethanol to rats, either in liquid diets as the only source of food or by gastric intubation while the animals are fed ad libitum, leads to the development of a hypermetabolic state of the liver. This hypermetabolic condition of the liver can be observed independently of the feeding state of the animals. The calorigenic effects produced by ethanol in the liver, as measured in liver slices, could be reproduced by a single large dose of epinephrine. Oxygen consumption by liver slices of animals given a 2-mg/kg dose of epinephrine bitartrate increased by 40 to 50 percent. In these livers all the extra oxygen consumption, but not the basal respiration, could be abolished by ouabain, an inhibitor of the sodium pump. Dinitrophenol did not affect the respiratory rate in the liver of epinephrine-treated animals while markedly increasing that in controls. In the liver of treated animals, the activatory effect of dinitrophenol could be recovered in the presence of ouabain. The calorigenic effect of epinephrine in the liver was found to be completely abolished by phentolamine (alpha adrenergic blocker) but was not modified by DL-propranolol (beta adrenergic blocker). Also, the calorigenic effects produced by epinephrine could not be seen in thyroidectomized animals or by incubating the liver slices in a calcium-free medium. Thyroidectomy and administration of phentolamine markedly reduced and adrenalectomy completely abolished the hypermetabolic state produced in the liver of rats by chronic administration of ethanol.