The role of endothelin in the pathogenesis of vasospasm following subarachnoid haemorrhage.
The role of endothelin in the pathogenesis of vasospasm following subarachnoid haemorrhage.
复制标题
内皮素在蛛网膜下腔出血后血管痉挛发病机制中的作用。
作者：
K. Ide;K. Yamakawa;T. Nakagomi;T. Sasaki;I. Saito;H. Kurihara;M. Yosizumi;Y. Yazaki;K. Takakura
本研究的目的是评价内皮素，一种新分离的内皮源性收缩肽，在离体和在体犬基底动脉的血管收缩活性。在离体条件下，10（-12）M（约3 × 10（-8）M）浓度的内皮素引起犬基底动脉的剂量依赖性收缩。最大张力大于40 mM KCl诱导的张力。EC 50值为1.9 +/- 0.6 X 10（-9）M（平均值+/- SEM）。10（-8）M尼卡地平或10（-5）M约10（-4）M罂粟碱可逆转内皮素引起的收缩。脑池内注射0.6 ~ 1.2 × 10 ~（-12）mol/kg的内皮素引起基底动脉双相收缩，持续24小时以上。收缩的初始阶段伴随着生命体征的显著变化，如血压急剧上升、心动过缓和呼吸停止。脑池内注射内皮素2.0 × 10 ~（-12）mol/kg也引起基底动脉的急性收缩。而脑池内注射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，内皮素诱导强而持久的脑动脉收缩。因此，内皮素可能在血管痉挛的发病机制中起重要作用。
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.