Uchida Y, Saotome M, Nomura A, Ninomiya H, Ohse H, Hirata F, Hasegawa S
Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan.
J Cardiovasc Pharmacol. 1991;17 Suppl 7:S210-2. doi: 10.1097/00005344-199100177-00060.
Our accompanying paper demonstrated that endothelin-1 (ET-1 constricts guinea pig airways directly and indirectly through mediators such as histamine and arachidonate metabolites. In order to exclude the role of mast cells in bronchoconstriction, we sensitized guinea pigs and challenged them in vitro with an antigen (ovalbumin). In the postanaphylactic trachea, ET-1 caused a transient relaxation followed by constriction. Such relaxation by ET was also observed in the tracheas constricted with carbamylcholine. The relaxation was completely blocked by nordihydroguaretic acid and AA861, lipooxygenase inhibitors, but not by indomethacin, a cyclooxygenase inhibitor, and FPL 55712, a leukotriene antagonist. Because the relaxation was not affected even in the presence of methylarginine, an inhibitor of NO synthesis, and superoxide dismutase, an enzyme for destroying NO radical, we concluded that ET-1 induces the relaxation of the tracheal muscles by producing lipooxygenase products, probably hydroperoxides of arachidonic acid.
我们的附随论文表明，内皮素 -1（ET-1）通过组胺和花生四烯酸代谢产物等介质直接和间接收缩豚鼠气道。为了排除肥大细胞在支气管收缩中的作用，我们使豚鼠致敏并在体外用抗原（卵清蛋白）对其进行激发。在过敏反应后的气管中，ET-1 引起短暂的舒张，随后是收缩。在用氨甲酰胆碱收缩的气管中也观察到 ET 引起的这种舒张。这种舒张被去甲二氢愈创木酸和 AA861（脂氧合酶抑制剂）完全阻断，但未被环氧化酶抑制剂吲哚美辛和白三烯拮抗剂 FPL 55712 阻断。由于即使在存在 NO 合成抑制剂甲基精氨酸和破坏 NO 自由基的酶超氧化物歧化酶的情况下，舒张也不受影响，我们得出结论，ET-1 通过产生脂氧合酶产物，可能是花生四烯酸的氢过氧化物，诱导气管肌肉舒张。
