Mechanism of the alcohol cyclic pattern: role of catecholamines.

The cause of the urinary alcohol level (UAL) cycle in rats fed ethanol at a constant rate has been shown to involve the hypothalamic-pituitary thyroid axis. Because the effect of thyroid hormone on the metabolic rate is augmented by catecholamines, the role of catecholamines was investigated by using the intragastric ethanol feeding model of alcoholic liver disease in which the UAL cycles over a 6- to 10-day period. The diet was supplemented with ephedrine and caffeine to test the hypothesis that the UAL cycle involves catecholamines. The UAL was followed to see whether the cycle was ablated by catecholamine supplements. Ethanol fed alone increased the blood levels of catecholamines significantly more than did ephedrine fed alone. However, blood catecholamine levels were significantly higher when ethanol was fed with ephedrine compared with the sum of ethanol and ephedrine fed alone. This indicated that the effect of ethanol and ephedrine were synergistic. The UAL cycle was completely ablated in the ethanol + ephedrine-fed rats. These rats tolerated a much higher dose of ethanol, indicating that they metabolized alcohol faster due to an increase in metabolic rate caused by ephedrine. In the ethanol + ephedrine-fed rats the liver pathology included significantly higher alanine amino transferase (ALT) in the blood and centrilobular ischemic necrosis in the liver. Necrosis was not present in the rats fed ephedrine alone. In conclusion, catecholamine supplements prevented the UAL cycle by increasing the metabolic rate to the point at which fluctuations in the metabolic rate caused by alcohol were prevented.