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>-3X10^-8M浓度下在体外引起犬、兔和猴基底动脉的剂量依赖性收缩。最大张力大于4OmM KCl引起的张力。(2)在蛛网膜下腔出血(SAH)暴露的犬基底动脉中激活ET-1诱导的收缩。(3)脑池内注射6-1.2X10^<- 12>mol/kg的ET-1引起犬基底动脉双相收缩，持续24小时以上。收缩初期伴有血压急剧升高、心动过缓、呼吸停止等生命体征的显着变化。(4)猫小脑延髓池注射ET-1，氢气清除法测定rCBF。注射后 180 分钟内每 30 分钟一次。 ET-1(10^<-11>mol和10^<-9>mol)诱导rCBF显着降低。 ET-1对rCBF的影响至少部分是由Ca^2+介导的，因为脑池内注射尼卡地平的预处理阻止了这种变化。(5)测量了SAH患者的血浆ET-1水平，浓度伴有血管痉挛的SAH患者血浆ET-1略高于无血管痉挛的SAH患者。 (6)特定拮抗剂对血管痉挛的影响在犬蛛网膜下腔出血模型中检测ET-1受体(BQ-485)对血管痉挛发生的影响。用 BQ-485 预处理 SAH 狗，第 7 天血管造影血管痉挛程度降低了约 15%。这些结果表明，脑血管内皮中产生的 ET-1 至少部分参与了血管痉挛的发生，尽管它不是主要因素。致病因素。