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

(1)内皮素(ET-1)在体外可引起犬、兔和猴的基底动脉收缩，呈剂量依赖性。(2)蛛网膜下腔出血(SAH)犬基底动脉内注射6-1.2×10~(-1)~(-12)~(-12)mol/kg ET-1可引起基底动脉双相收缩，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著变化。(4)猫枕大池注射ET-1，用氢清除法测定注射前及注射后每30min一次的局部脑血流量，持续180min。ET-1(10^&lt；-11；Moland 10^&lt；-9&gt；mol)可引起rCBF显著降低。ET-1对rCBF的影响至少部分是由Ca~(2+)和Gt~(2+)介导的，因为脑室注射尼卡地平可阻止这种变化。(5)测定SAH患者血浆ET-1水平，发现伴有血管痉挛的SAH患者血浆ET-1浓度略高于无血管痉挛的SAH患者。(6)在犬SAH模型上观察ET-1受体特异性拮抗剂(BQ-485)对血管痉挛发生的影响。BQ-485可使SAH犬血管造影后第7天的血管痉挛程度降低约15%。结果表明，脑血管内皮细胞产生的ET-1虽然不是主要致病因素，但至少部分参与了血管痉挛的发生。

(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.