Förstermann U, Neufang B
Prostaglandins. 1984 Feb;27(2):181-93. doi: 10.1016/0090-6980(84)90072-8.
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.
乙酰胆碱（ACh）通过一种依赖于完整内皮的机制使预先收缩的兔主动脉条舒张，可能是通过释放一种未知的内皮舒张因子（ERF）。这种舒张作用被脂氧合酶抑制剂去甲二氢愈创木酸（10⁻⁵ M）完全抑制，但不被环氧化酶抑制剂吲哚美辛（10⁻⁵ M）抑制。发现主动脉条释放少量具有白三烯样活性的物质。其对豚鼠回肠的作用被FPL 55712（10⁻⁶ M）拮抗。然而，FPL 55712（10⁻⁶ - 10⁻⁴ M）并未改变兔主动脉条对ACh的反应。此外，当用马来酸二乙酯或2 - 环己烯 - 1 - 酮（均为10⁻³ M）孵育主动脉条以降低细胞内谷胱甘肽（GSH）浓度时，仍可引发血管舒张反应。发现白三烯（LT）C4和LTD4（10⁻⁹ - 10⁻⁶ M）在基础张力或诱导张力下对主动脉条无效。LTE4（10⁻⁹ - 10⁻⁷ M）也是如此。然而，在10⁻⁶ M时，LTE4可引起血管组织轻微舒张。基于所讨论的原因，这可能是一种独立于内源性ERF作用的药理作用（例如，高细胞外GSH浓度抑制LTE4前体LTD4的形成并不能逆转ACh诱导的血管舒张）。从这些数据得出结论，C - 6 - sulfidopeptide白三烯虽然可能由血管组织产生，但不太可能参与ACh诱导的兔主动脉舒张。
