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.
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D003512:Cyclohexanones / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008298:Maleates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D013189:SRS-A / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D003512:Cyclohexanones; D008298:Maleates; D010455:Peptides; D013189:SRS-A; C028215:2-cyclohexen-1-one; C014476:diethyl maleate; D000109:Acetylcholine; D009638:Norepinephrine; D007213:Indomethacin