Ishikawa T, Yanagisawa M, Kimura S, Goto K, Masaki T
Department of Pharmacology, University of Tsukuba, Ibaraki, Japan.
Am J Physiol. 1988 Oct;255(4 Pt 2):H970-3. doi: 10.1152/ajpheart.1988.255.4.H970.
Endothelin (ET), a novel 21-amino acid peptide isolated from the culture supernatant of porcine aortic endothelial cells, has been shown to be the most potent of all known vasoconstrictor substances. The purpose of the present study was to investigate the effects and the mode of actions of ET on the heart. ET exerted a positive inotropic effect in a dose-dependent manner on the electrically driven left atria of guinea pigs. The ET-induced response was of slow onset and characteristically long lasting. The half-maximal effective dose of the ET-induced response was about 1 nM, indicating that ET is one of the most potent cardiotonic substances. The response was presumably caused through direct actions of ET on the myocytes, since adrenergic, histaminergic, and serotonergic antagonists showed no effect on the response. The dose-response relationship of ET for the positive inotropic effect was displaced to the right in a parallel fashion by 0.3 microM nicardipine. In the left atria depolarized with 22 mM KCl, ET produced gradually increasing contractions in conjunction with the slow response action potentials in response to the electrical pacing. These results suggest that the ET-induced response on the left atria is intimately related to the influx of extracellular Ca2+.
内皮素（ET）是一种从猪主动脉内皮细胞培养上清液中分离出的由21个氨基酸组成的新型肽，已被证明是所有已知血管收缩物质中最有效的。本研究的目的是探讨ET对心脏的作用及其作用方式。ET对豚鼠电驱动的左心房具有剂量依赖性的正性肌力作用。ET诱导的反应起效缓慢且持续时间长。ET诱导反应的半数最大有效剂量约为1 nM，表明ET是最有效的强心物质之一。该反应可能是由ET对心肌细胞的直接作用引起的，因为肾上腺素能、组胺能和5-羟色胺能拮抗剂对该反应无影响。0.3 microM尼卡地平使ET正性肌力作用的剂量反应关系平行右移。在用22 mM KCl使左心房去极化的情况下，ET随着电起搏时缓慢反应动作电位的出现逐渐增加收缩力。这些结果表明，ET对左心房的诱导反应与细胞外Ca2+内流密切相关。
