Ide K, Yamakawa K, Nakagomi T, Sasaki T, Saito I, Kurihara H, Yosizumi M, Yazaki Y, Takakura K
Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan.
Neurol Res. 1989 Jun;11(2):101-4. doi: 10.1080/01616412.1989.11739870.
The purpose of the present study was to evaluate the vasocontractile activity of endothelin, a newly isolated endothelium-derived constrictor peptide, in canine basilar arteries in vitro and in vivo. Endothelin at concentrations of 10(-12) M approximately 3 X 10(-8) M elicited dose-dependent contractions of canine basilar arteries in vitro. The maximum tension was larger than that induced by 40 mM KCl. The EC50 value was 1.9 +/- 0.6 X 10(-9) M (mean +/- SEM). The endothelin-induced contraction was reversed by 10(-8) M nicardipine or 10(-5) M approximately 10(-4) M papaverine. An intracisternal injection of 0.6 approximately 1.2 X 10(-12) mol/kg of endothelin caused biphasic contraction of the basilar artery lasting for more than 24 h. The initial phase of the contraction accompanied remarkable changes in vital signs such as an acute rise of blood pressure, bradycardia and respiratory arrest. An intracisternal injection of 2.0 X 10(-12) mol/kg of endothelin also induced acute contraction of the basilar artery. However, all of the dogs which received an intracisternal injection of 2.0 X 10(-12) mol/kg of endothelin died from sustained respiratory insufficiency. The present results demonstrate that endothelin induces strong and long-lasting contractions of cerebral arteries. Therefore, endothelin may play an important role in the pathogenesis of vasospasm.
本研究的目的是在体外和体内评估内皮素（一种新分离出的内皮源性收缩肽）对犬基底动脉的血管收缩活性。浓度为10^(-12)M至约3×10^(-8)M的内皮素在体外可引起犬基底动脉剂量依赖性收缩。最大张力大于40mM氯化钾所诱导的张力。半数有效浓度（EC50）值为1.9±0.6×10^(-9)M（平均值±标准误）。内皮素诱导的收缩可被10^(-8)M尼卡地平或10^(-5)M至约10^(-4)M罂粟碱逆转。脑池内注射0.6至1.2×10^(-12)mol/kg的内皮素可引起基底动脉双相收缩，持续超过24小时。收缩的初始阶段伴有生命体征的显著变化，如血压急性升高、心动过缓和呼吸停止。脑池内注射2.0×10^(-12)mol/kg的内皮素也可诱导基底动脉急性收缩。然而，所有接受脑池内注射2.0×10^(-12)mol/kg内皮素的犬均死于持续性呼吸功能不全。目前的结果表明，内皮素可诱导脑动脉强烈且持久的收缩。因此，内皮素可能在血管痉挛的发病机制中起重要作用。
