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We used the intragastric feeding rat model for alcohol liver disease to investigate the relationship between endothelin and pathologic liver injury. Rats were fed the following diets for periods of 1, 2 and 4 weeks: corn oil plus ethanol (CE), corn oil plus dextrose (CD) and saturated fat plus ethanol (SE). Plasma endothelin levels were significantly higher in the CE group compared to the other groups at all time periods studied. The CE animals, also, developed pathologic liver injury which is in contrast to the SE and CD animals which showed no pathologic changes. We propose that endothelin, because of its powerful vasoconstrictive effects, leads to a reduction in hepatic blood flow which is important in the pathogenesis of alcoholic liver disease.

We used the intragastric feeding rat model for alcoholic liver disease to investigate the relationship between prostacyclin and liver injury. Rats were fed the following diets for periods ranging from 1 to 8 weeks: corn oil plus ethanol (CO+E), corn oil plus dextrose (CO+D), saturated fat plus ethanol (SF+E) and saturated fat plus dextrose (SF+D). Prostacyclin production (assessed by 6-ketoprostaglandin F1 alpha) by liver non-parenchymal cells decreased steadily over the 8 week period in animals fed CO+E (liver injury present) whereas in animals fed SF+E (no liver injury) there was no change in prostacyclin production. Plasma levels of 6-ketoprostaglandin F1 alpha were also significantly lower in the CO+E group compared to the other groups studied. We propose that decreased prostacyclin production by liver non-parenchymal cells may contribute to the hepatotoxic effect of ethanol.