Reid J J, Lieu A T, Rand M J
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Eur J Pharmacol. 1991 Mar 5;194(2-3):173-81. doi: 10.1016/0014-2999(91)90102-v.
In isolated spontaneously beating right and left atria and in electrically driven left atrium from rat, endothelin-1 increased the rate and force of contraction, but significantly decreased the positive chronotropic and inotropic responses to sympathetic nerve stimulation. The decrease may be partly dependent on the positive cronotropic and inotropic effects of endothelin-1, since other agents with chronotropic activity (noradrenaline, isoprenaline, serotonin and Bay k 8644) also decreased stimulation-induced chronotropic responses. Endothelin-1 caused a significant rightward shift of the linear portion of the log concentration-response curve for the chronotropic actions of noradrenaline and isoprenaline. The changes in the log concentration-response curve were not a consequence of the direct chronotropic effect of endothelin-1, since they were still evident when the chronotropic action of endothelin-1 was offset by carbachol. Furthermore, the chronotropic agent, Bay k 8644, did not shift the linear portion of the log concentration-response curves for noradrenaline and isoprenaline. The mechanism of the effects of endothelin-1 in rat atria is not known, but they were not changed by blockade of alpha-adrenoceptors or of L-type voltage-sensitive Ca2+ channels.
在大鼠离体的自发搏动的右心房和左心房以及电驱动的左心房中，内皮素-1增加了收缩速率和力量，但显著降低了对交感神经刺激的正性变时性和变力性反应。这种降低可能部分依赖于内皮素-1的正性变时性和变力性作用，因为其他具有变时活性的药物（去甲肾上腺素、异丙肾上腺素、5-羟色胺和Bay k 8644）也降低了刺激诱导的变时反应。内皮素-1使去甲肾上腺素和异丙肾上腺素变时作用的对数浓度-反应曲线的线性部分显著右移。对数浓度-反应曲线的变化不是内皮素-1直接变时作用的结果，因为当内皮素-1的变时作用被卡巴胆碱抵消时，这些变化仍然明显。此外，变时药物Bay k 8644并没有使去甲肾上腺素和异丙肾上腺素的对数浓度-反应曲线的线性部分发生移动。内皮素-1对大鼠心房作用的机制尚不清楚，但α-肾上腺素能受体或L型电压敏感性Ca2+通道的阻断并没有改变这些作用。
