THE ROLE OF ENDOTHELIUM-DERIVED CONSTRICTING FACTOR(ENDOTHELIN) IN THE PATHOGENESIS OF CEREBRAL VASOSPASM

内皮源性收缩因子（内皮素）在脑血管痉挛发病中的作用

基本信息

批准号：
01480349
负责人：
SASAKI Tomio
金额：
$ 3.14万
依托单位：
UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1991
项目状态：
已结题

项目摘要

(1)Endothelin(ET-1) at concentrations of 10^<-12>-3XlO^<-8>M elicited dose-dependent contractions of canine, rabbit and monkey basilar arteries in vitro. The maximum tension was larger than that induced by 4OmM KCl.(2)ET-1-induced contarction was activated in the canine basilar artery exposed to subarachnoid hemorrhage(SAH).(3)An intracisternal injection of 6-1.2X10^<-12>mol/kg of ET-1 caused biphasic contraction of the canine basilar artery lasting for more than 24 hours. The initial phase of the contraction accompanied remarkable changes in vital signs such as an acute rise of blood pressure, bradycardia and respiratory arrest.(4)ET-1 was injected into the cisterna magna of cats and rCBF was measured by the hydrogen clearance method before and every 30 minutes for 180 minutes after the injection. ET-1(10^<-11>moland 10^<-9>mol) induced a significant decrease in rCBF. The effects of ET-1 on rCBF were mediated, at least in part, by Ca^<2+>, because pretreatment with intracisternally injected nicardipine prevented the changes.(5)Plasma levels of ET-1 were measured in SAH patients, Concentrations of plasma ET-1 in SAH patients with va sospasm were a little higher than those in SAH patients without vasospasm.(6)The effects of a specific antagonist for ET-1 receptor(BQ-485) on the occurrence of vasospasm were examined in the canine SAH models. Pretreatment of SAH dogs with BQ-485 decreased the degree of angiographic vasospasm by about 15% on Day 7.These results indicate that ET-1 produced in cerebrovascular endothelium contpibute to the occurrence of vasospasm at least in part, although it is not a main causative factor.

（1）内皮素（ET-1）在10^<-12> -3xlo^<-8> m的浓度下引起犬，兔和猴子基底动脉的剂量依赖性收缩。最大张力大于4omm kcl诱导的（2）ET-1诱导的张力在暴露于蛛网膜下腔出血（SAH）的犬基底动脉中。收缩的初始阶段伴随着生命体征的显着变化，例如血压的急性升高，心动过缓和呼吸阻滞。（4）ET-1在注入前和每30分钟之前，每30分钟将ET-1注射到猫的水库中，并通过氢清除法测量RCBF。 ET-1（10^<-11> moland 10^<-9> mol）诱导RCBF显着降低。至少部分地通过Ca^<2+>介导了ET-1对RCBF的影响，因为诊所内注射的尼卡丁胺预处理阻止了这些变化。（5）SAH患者在SAH患者中测量了ET-1的血浆水平，SAH患者在SAH Sospasm中的血浆ET-1浓度比SAH的患者更高，而不是SAH的患者，而不是SAH的效果。在犬SAH模型中检查了血管痉挛发生的受体（BQ-485）。使用BQ-485的SAH狗预处理使血管造影血管痉挛的程度降低了约15％。这些结果表明，在脑血管内皮内皮中产生的ET-1至少在某种程度上至少在某种程度上发生了血管痉挛，尽管这不是主要的导致因子。