Touyz R M, Fareh J, Thibault G, Larivière R, Schiffrin E L
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Québec, Canada.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S297-9.
Endothelin-1 (ET-1) may exert inotropic and chronotropic effects in cardiac muscle by modulating intracellular Ca2+. This study assesses effects of ET-1 on intracellular free Ca2+ concentration ([Ca2+]i) in neonatal and adult rat cardiomyocytes. [Ca2+]i was measured by Fura 2 methodology. ET receptor subtypes were determined by binding studies. ET-1 increased neonatal and adult [Ca2+]i and spike frequency in a dose-dependent manner. It decreased [Ca2+]i amplitude in neonatal cardiomyocytes but had no effect on [Ca2+]i amplitude in adult cells. The ET(A) receptor antagonist BQ-123 reduced ET-1-induced responses and the ETB receptor agonist IRL-1620 increased [Ca2+]i. ET-1 binding studies demonstrated 85% displacement by BQ-123 and 15% by the ETB receptor agonist sarafotoxin S6c, suggesting a predominance of ET(A) receptors. These data demonstrate that in neonatal and adult cardiomyocytes ET-1 has stimulatory effects on [Ca2+]i which are mediated predominantly via ET(A) receptors. Therefore, ET-1 may influence cardiac development and function.
内皮素-1（ET-1）可能通过调节细胞内钙离子来发挥对心肌的变力性和变时性作用。本研究评估了ET-1对新生大鼠和成年大鼠心肌细胞内游离钙离子浓度（[Ca2+]i）的影响。采用Fura 2方法测量[Ca2+]i。通过结合研究确定ET受体亚型。ET-1以剂量依赖性方式增加新生大鼠和成年大鼠的[Ca2+]i及动作电位频率。它降低了新生心肌细胞的[Ca2+]i幅度，但对成年细胞的[Ca2+]i幅度无影响。ET(A)受体拮抗剂BQ-123可降低ET-1诱导的反应，而ETB受体激动剂IRL-1620可增加[Ca2+]i。ET-1结合研究表明，BQ-123可置换85%的结合，ETB受体激动剂沙拉毒素S6c可置换15%的结合，这表明ET(A)受体占主导地位。这些数据表明，在新生大鼠和成年大鼠心肌细胞中，ET-1对[Ca2+]i具有刺激作用，且主要通过ET(A)受体介导。因此，ET-1可能影响心脏发育和功能。
