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

(1)内皮素（ET-1）浓度为10^<-12>-3XlO^<-8>M时，可引起犬、兔和猴基底动脉的剂量依赖性收缩。最大张力大于40mm KCl诱导的张力。(2)暴露于蛛网膜下腔出血（SAH）的犬基底动脉激活et -1诱导的收缩。(3)腹腔注射6-1.2X10^<-12>mol/kg ET-1可引起犬基底动脉双相收缩，持续24小时以上。宫缩初期伴有显著的生命体征变化，如血压急剧升高、心动过缓和呼吸骤停。(4)将ET-1注射到猫大池，注射前和注射后180分钟内，每30分钟用氢清除法测定rCBF。ET-1（10^<-11>mol和10^<-9>mol）诱导rCBF显著降低。ET-1对rCBF的影响至少部分是由Ca^<2+>介导的，因为内源性注射尼卡地平的预处理阻止了这种变化。(5)测定SAH患者血浆ET-1水平，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模型中检测了ET-1受体特异性拮抗剂（BQ-485）对血管痉挛发生的影响。BQ-485预处理SAH犬后，第7天血管痉挛程度降低约15%。这些结果表明，在脑血管内皮中产生的ET-1虽然不是主要的致病因素，但至少在一定程度上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.