Positive Inotropic and Vasoconstrictive Effects of Endothelin‐1 in in vivo and in vitro Experiments: Characteristics and the Role of L‐Type Calcium Channels
Positive Inotropic and Vasoconstrictive Effects of Endothelin‐1 in in vivo and in vitro Experiments: Characteristics and the Role of L‐Type Calcium Channels
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内皮素-1在体内和体外实验中的正性肌力和血管收缩作用：L型钙通道的特征和作用
DOI：
10.1097/00005344-198900135-00027
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发表时间：
1989
影响因子：
3
通讯作者：
N. Shimamoto
中科院分区：
文献类型：
--
作者：
Toshifumi Watanabe;K. Kusumoto;T. Kitayoshi;N. Shimamoto
本研究通过在体血流动力学模型和离体动脉及心脏组织研究了内皮素-1（ET-1）的心血管效应。静脉注射ET-1（30-300 pmol/kg）后，血流动力学改变明显减轻。犬的血压、心输出量和心室收缩力增加。犬冠状动脉和兔胸主动脉环对ET-1（10 ~（-10）M及以上）有缩血管反应，EC_（50）为3-10 × 10 ~（-9）M。硝苯地平10-5 M不能完全逆转这些作用。ET-1在10-10 μ M时对兔乳头肌有正性肌力作用。使动作电位时程延长16%，产生的张力增加180%（10-8 M）。相比之下，湾K 8644（10-7 M）产生类似的延长（17%）的持续时间，只有37%的张力增加。这表明这两种药物的正性肌力作用机制不同。我们的结论是，ET-1具有正性肌力和血管收缩作用，这些ET-1诱导的心室肌和动脉收缩不能完全解释通过电压依赖性钙通道电流的增加。
Summary Cardiac and vascular effects of endothelin-1 (ET-1) were studied in hemodynamic models in vivo and in isolated artery and heart tissues. The hemodynamic changes induced by ET-1 (30–300 pmol/kg i.v.) in dogs were increases in blood pressure, cardiac output, and ventricular contractility. Ring preparations of canine coronary artery and rabbit thoracic aorta showed vasoconstrictive responses to ET-1 (10–10 M and over) with an EC50 of 3–10 $$ 10–9 M. Nifedipine 10–5 M did not reverse these effects completely. ET-1 had positive inotropic effects from 10–10 M in rabbit papillary muscles. It lengthened the action potential duration by 16% and increased the developed tension by 180% (10–8 M). In contrast, Bay K 8644 (10–7 M) produced similar lengthening (17%) in the duration with only a 37% increase in the tension. This suggests a difference in the mechanisms of the positive inotropic effects between these two agents. We conclude that ET-1 has positive inotropic and vasoconstrictive effects, and that these ET-1-induced contractions in ventricular muscles and arteries cannot be explained thoroughly by the increase in currents through voltage-dependent calcium channels.