The synthesis of N-acetyl-leukotriene E4 and its effects on cardiovascular and respiratory function of the anesthetized pig.

The effects of the putative biliary metabolite of the peptido-leukotrienes, N-acetyl-leukotriene (LT) E4 has been investigated in the anesthetized pig. Intravenous bolus doses of synthetic N-acetyl-LTE4 produced minimal respiratory and cardiovascular actions in the pig. N-acetyl-LTE4 was approximately 100-fold less active than LTC4. The actions of N-acetyl-LTE4 were not blocked by pretreatment of the animals with indomethacin (5 mg/kg iv) or with a selective LTD4 antagonist L-649,923 (5 mg/kg plus 2 mg/kg/hr iv). In summary, N-acetyl-LTE4 exerts weak actions in the pig which is consistent with the acetylation process being a mechanism of detoxification.