Warner T D, Mitchell J A, de Nucci G, Vane J R
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England.
J Cardiovasc Pharmacol. 1989;13 Suppl 5:S85-8; discussion S102. doi: 10.1097/00005344-198900135-00021.
We have previously shown that porcine endothelin (ET-1) releases endothelium-derived relaxing factor (EDRF) in the rat isolated perfused mesentery. Here we show that both ET-1 (1-100 pmol) and rat endothelin (ET-3, 1-300 pmol) release EDRF in this preparation and that ET-1 releases EDRF from the luminally perfused aorta of the rabbit. Furthermore, we confirm that, as a pressor agent, ET-1 is greater than 10 times more potent than ET-3. Vasodilatations in the rat isolated perfused mesentery in response to ET-1 and ET-3 were due to the release of EDRF since they were inhibited by removal of the endothelium, methylene blue (100 microM), or hemoglobin (30 microM). ET-3 was more selective than ET-1 as a vasodilator because ET-1 induced vasodilatations were limited and in the higher doses overwhelmed by concurrent vasoconstrictions. Release of EDRF from the rabbit aorta in response to ET-1 but not to other agonists (acetylcholine, substance P, or adenosine diphosphate) was potentiated by infusion of potassium chloride (3 mM). Bay K 8644 failed to release EDRF in either system or to constrict the nondepolarized rat mesentery. Thus, both ET-1 and ET-3 release EDRF by activation of receptors or channels that differ from dihydropyridine-sensitive calcium channels.
我们先前已表明，猪内皮素（ET-1）可在大鼠离体灌注肠系膜中释放内皮衍生舒张因子（EDRF）。在此我们表明，ET-1（1 - 100 pmol）和大鼠内皮素（ET-3，1 - 300 pmol）均可在此制备物中释放EDRF，且ET-1可从兔的腔内灌注主动脉释放EDRF。此外，我们证实，作为一种升压剂，ET-1的效力比ET-3强10倍以上。大鼠离体灌注肠系膜中对ET-1和ET-3的血管舒张是由于EDRF的释放，因为去除内皮、加入亚甲蓝（100 microM）或血红蛋白（30 microM）均可抑制这种舒张。ET-3作为血管舒张剂比ET-1更具选择性，因为ET-1诱导的血管舒张有限，且在高剂量时会被同时发生的血管收缩所掩盖。通过输注氯化钾（3 mM）可增强兔主动脉对ET-1而非其他激动剂（乙酰胆碱、P物质或二磷酸腺苷）释放EDRF的反应。Bay K 8644在任一系统中均未能释放EDRF，也未能使未去极化的大鼠肠系膜收缩。因此，ET-1和ET-3均通过激活不同于二氢吡啶敏感钙通道的受体或通道来释放EDRF。
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