Suzuki S, Kajikuri J, Suzuki A, Itoh T
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Circ Res. 1991 Nov;69(5):1361-8. doi: 10.1161/01.res.69.5.1361.
The effects of endothelin-1 (ET-1) on endothelial cells from the porcine coronary artery were investigated using cascade bioassay and radioimmunoassay methods. For comparison, endothelial cells from the rabbit abdominal aorta were also used. Freshly isolated endothelial cells were perfused with Krebs' solution. Liberation of vasodilatory substances was detected under bioassay conditions by measuring the relaxing activity of the perfusate on endothelium-denuded strips of the porcine coronary artery contracted with ET-1. The perfusate in the absence of ET-1 slightly inhibited the contraction, suggesting that endothelial cells spontaneously release vasorelaxing substances. After application of ET-1, the perfusate-induced relaxation drastically increased. Oxyhemoglobin completely abolished the relaxation induced by perfusate from endothelial cells of the rabbit abdominal aorta but only marginally attenuated the relaxation induced by perfusate from endothelial cells of the porcine coronary artery. In contrast, indomethacin significantly attenuated the relaxation induced by perfusate from the endothelial cells of the porcine coronary artery. In endothelium-intact strips of the porcine coronary artery, ET-1 significantly increased the concentration of 6-ketoprostaglandin F1 alpha but did not modify the cellular concentration of either cAMP or cGMP. It is concluded that ET-1 augments the release of vasorelaxing factors from endothelial cells both in the porcine coronary artery and in the rabbit abdominal aorta and that the major vasorelaxing substance derived from endothelial cells may be different in these two blood vessels. Prostaglandin I2 in the former and nitric oxide in the latter are suggested as possible candidates. The vasorelaxation induced by prostaglandin I2 may not be mediated by cAMP-dependent mechanisms in the porcine coronary artery.
采用级联生物测定法和放射免疫测定法研究了内皮素-1（ET-1）对猪冠状动脉内皮细胞的影响。作为对照，还使用了兔腹主动脉的内皮细胞。将新鲜分离的内皮细胞用 Krebs 溶液灌注。在生物测定条件下，通过测量灌注液对用 ET-1 收缩的猪冠状动脉去内皮条的舒张活性来检测血管舒张物质的释放。在无 ET-1 时，灌注液轻微抑制收缩，提示内皮细胞可自发释放血管舒张物质。应用 ET-1 后，灌注液诱导的舒张作用显著增强。氧合血红蛋白完全消除了兔腹主动脉内皮细胞灌注液诱导的舒张作用，但仅轻微减弱了猪冠状动脉内皮细胞灌注液诱导的舒张作用。相反，吲哚美辛显著减弱了猪冠状动脉内皮细胞灌注液诱导的舒张作用。在猪冠状动脉内皮完整的条带中，ET-1 显著增加了 6-酮前列腺素 F1α的浓度，但未改变细胞内 cAMP 或 cGMP 的浓度。结论是，ET-1 增强了猪冠状动脉和兔腹主动脉内皮细胞释放血管舒张因子的能力，且这两种血管中内皮细胞衍生的主要血管舒张物质可能不同。提示前者为前列腺素 I2，后者为一氧化氮。前列腺素 I2 诱导的血管舒张在猪冠状动脉中可能不通过 cAMP 依赖性机制介导。
