Tanaka Y, Shigenobu K, Nakayama K
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi-City, Chiba, Japan.
Res Commun Mol Pathol Pharmacol. 2001 Jul;109(1-2):95-101.
The present study was performed to investigate the effects of endothelin-1 (ET-1) on the myogenic contraction in response to mechanical stimulation in cerebral artery. Quick stretch at a rate of 10 cm/sec with the amount of 10 - 40% of the initial muscle length (=100%) produced a myogenic contraction in canine cerebral artery. ET-1 at 30 pM, which itself produces a small contraction corresponding to about 15% of the maximal response, potentiated stretch-induced contraction. By contrast, ET-1 at concentrations over 100 pM suppressed the stretch-induced tone. The potentiated component of stretch-induced tone in the presence of 30 pM ET-1 was largely attenuated by Ca2+ channel blockers, nimodipine (1 microM) or diltiazem (1 microM). These findings suggest that lower concentrations (pM range) of ET- 1 potentiates myogenic tension development of cerebral artery in response to mechanical stretch possibly via an increased Ca2+ influx through voltage-gated Ca2+ channel.
本研究旨在探讨内皮素-1(ET-1)对脑动脉机械刺激引起的肌源性收缩的影响。以10厘米/秒的速度进行快速拉伸,拉伸幅度为初始肌肉长度(=100%)的10%-40%,可在犬脑动脉中产生肌源性收缩。30皮摩尔的ET-1本身会产生相当于最大反应约15%的小收缩,它增强了拉伸诱导的收缩。相比之下,浓度超过100皮摩尔的ET-1会抑制拉伸诱导的张力。在存在30皮摩尔ET-1的情况下,拉伸诱导张力的增强成分在很大程度上被钙通道阻滞剂尼莫地平(1微摩尔)或地尔硫䓬(1微摩尔)减弱。这些发现表明,较低浓度(皮摩尔范围)的ET-1可能通过增加电压门控钙通道的钙内流,增强脑动脉对机械拉伸的肌源性张力发展。