C-6-sulfidopeptide leukotrienes are unlikely to be involved in the endothelium dependent relaxation of rabbit aorta by acetylcholine.

Acetylcholine (ACh) induced dilation of precontracted strips of rabbit aorta by a mechanism dependent on an intact endothelium, probably by releasing an unknown endothelial relaxing factor (ERF). The relaxation was completely inhibited by the lipoxygenase inhibitor nordihydroguaiaretic acid (10(-5) M) but not by the cyclooxygenase inhibitor indomethacin (10(-5) M). The aortic strips were found to release small amounts of a material with a leukotriene-like activity. Its action on the guinea pig ileum was antagonized by FPL 55712 (10(-6) M). However, FPL 55712 (10(-6) - 10(-4) M) did not alter the response of rabbit aortic strips to ACh. Also when decreasing intracellular concentrations of glutathion (GSH) by incubating the strips with diethylmaleat or 2-cyclohexen-1-one (both 10(-3) M) the vasodilator response could still be elicited. Leukotriene (LT) C4 and LTD4 (10(-9) - 10(-6) M) were found to be ineffective on aortic strips under basal or induced tension. The same held true for LTE4 (10(-9) - 10(-7) M). At 10(-6) M, however, LTE4 induced slight relaxations of the vascular tissues. For reasons discussed this is likely to be a pharmacological action independent of the effects of endogenous ERF (e.g. inhibition of the formation of the LTE4 precursor LTD4 by high extracellular GSH concentrations did not reverse the ACh-induced vasodilation). It is concluded from these data, that C-6-sulfidopeptide leukotrienes, although probably produced by vascular tissue, are unlikely to be involved in the ACh-induced relaxation of rabbit aorta.