Miyauchi T, Tomobe Y, Shiba R, Ishikawa T, Yanagisawa M, Kimura S, Sugishita Y, Ito I, Goto K, Masaki T
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Circulation. 1990 Jun;81(6):1874-80. doi: 10.1161/01.cir.81.6.1874.
Endothelin, a recently discovered endothelium-derived peptide, has been reported to produce potent vasoconstriction in various vessels of experimental animals. To study the involvement of endothelin in the regulation of vascular tonus in humans, isolated human mesenteric arteries were investigated by both pharmacological and immunohistochemical methods. The vasoconstrictor action of endothelin-1 was examined on ring segments of human mesenteric arteries. Endothelin-1 induced a slowly developing and sustained contraction, with an EC50 value (half-maximal effective concentration) of 2.9 x 10(-9) M, two orders of magnitude smaller than that of norepinephrine (EC50 of 3.9 x 10(-7) M), indicating that the vasoconstrictor action of endothelin-1 is about 100 times more potent than that of norepinephrine. The contractile effect of endothelin-1 was affected neither by adrenergic, cholinergic, histaminergic, nor serotonergic antagonists, nor by inhibitors of arachidonic acid metabolism. The vasoconstrictor response to endothelin-1 was effectively antagonized by nicardipine, a dihydropyridine Ca2+ channel blocker. Endothelin-1 profoundly augmented contractile response to Ca2+ in partially depolarized tissues. Immunohistochemical studies revealed for the first time that endothelin-like immunoreactivity was localized in endothelial cells of human mesenteric artery. The results of the present study indicate that endothelin-1 is one of the most potent vasoconstrictors in the human mesenteric artery and that it induces vasoconstriction via an ultimately accelerating Ca2+ influx through voltage-dependent Ca2+ channels. Since endothelin-1 can be located in human endothelial cells, it may play an important physiological or pathophysiological role.
内皮素是最近发现的一种内皮源性肽，据报道它可在实验动物的各种血管中产生强烈的血管收缩作用。为了研究内皮素在人体血管张力调节中的作用，采用药理学和免疫组织化学方法对分离的人肠系膜动脉进行了研究。检测了内皮素 -1对人肠系膜动脉环段的血管收缩作用。内皮素 -1诱导了缓慢发展且持续的收缩，其半数有效浓度（EC50）值为2.9×10⁻⁹ M，比去甲肾上腺素的EC50值（3.9×10⁻⁷ M）小两个数量级，这表明内皮素 -1的血管收缩作用比去甲肾上腺素强约100倍。内皮素 -1的收缩作用既不受肾上腺素能、胆碱能、组胺能或5-羟色胺能拮抗剂的影响，也不受花生四烯酸代谢抑制剂的影响。尼卡地平（一种二氢吡啶类钙通道阻滞剂）可有效拮抗内皮素 -1引起的血管收缩反应。内皮素 -1显著增强了部分去极化组织对钙离子的收缩反应。免疫组织化学研究首次发现，内皮素样免疫反应性定位于人肠系膜动脉的内皮细胞中。本研究结果表明，内皮素 -1是人体肠系膜动脉中最有效的血管收缩剂之一，它通过最终加速钙离子经电压依赖性钙通道内流来诱导血管收缩。由于内皮素 -1可存在于人体内皮细胞中，它可能发挥重要的生理或病理生理作用。
