Förstermann U, Neufang B
Eur J Pharmacol. 1984 Aug 3;103(1-2):65-70. doi: 10.1016/0014-2999(84)90190-0.
Acetylcholine (ACh) caused concentration-dependent relaxation of strips of rabbit thoracic aorta precontracted with noradrenaline if the endothelium was intact. More than ten-fold higher concentrations of ACh also stimulated the release of prostacyclin (PGI2) and PGE2 from the strips. De-endothelialized strips released much smaller amounts of prostaglandins and contracted slightly to ACh. The endothelium-dependent vasodilation was resistant to cyclooxygenase inhibition by indomethacin, flurbiprofen and diclofenac. However, it could be reversed by six different inhibitors of lipoxygenase (nordihydroguaiaretic acid, phenidone, eicosatetraynoic acid, nafazatrom, compound BW 755C and caffeic acid). BW 755C and caffeic acid, a selective inhibitor of 5-lipoxygenase, had comparatively weak effects on the relaxation. Eicosatetraynoic acid, which probably does not inhibit C-5-lipoxygenase, completely reversed the effect of ACh. It is concluded that ACh relaxes strips of rabbit aorta by a mechanism in involving a non-cyclooxygenase metabolite of arachidonic acid of endothelial origin. This compound is probably not a product of C-5-lipoxygenase.
如果内皮完整，乙酰胆碱（ACh）可使去甲肾上腺素预收缩的兔胸主动脉条产生浓度依赖性舒张。浓度高于十余倍的ACh还可刺激主动脉条释放前列环素（PGI2）和前列腺素E2（PGE2）。去内皮的主动脉条释放的前列腺素量少得多，且对ACh产生轻微收缩反应。内皮依赖性血管舒张对吲哚美辛、氟比洛芬和双氯芬酸的环氧化酶抑制作用具有抗性。然而，它可被六种不同的脂氧合酶抑制剂（去甲二氢愈创木酸、非那吡啶、二十碳四烯炔酸、萘呋胺酯、化合物BW 755C和咖啡酸）逆转。BW 755C和5-脂氧合酶的选择性抑制剂咖啡酸对舒张作用的影响相对较弱。可能不抑制C-5-脂氧合酶的二十碳四烯炔酸可完全逆转ACh的作用。结论是，ACh通过一种涉及内皮来源花生四烯酸的非环氧化酶代谢产物的机制使兔主动脉条舒张。该化合物可能不是C-5-脂氧合酶的产物。
