Hansen-Schwartz Jacob, Hoel Natalie Løvland, Zhou Mingfang, Xu Cang-Bao, Svendgaard Niels Aage, Edvinsson Lars
Department of Internal Medicine, Lund University Hospital, Lund, Sweden.
Neurosurgery. 2003 May;52(5):1188-94; 1194-5.
Inspired by organ culture-induced changes in the vascular endothelin (ET) receptor population, we investigated whether such changes occur in cerebral arteries in a rat subarachnoid hemorrhage (SAH) model.
SAH was induced with injection of 250 microl of blood into the prechiasmatic cistern. After 2 days, the middle cerebral artery, basilar artery, and posterior communicating artery were harvested. Pharmacological studies were performed in vitro, and levels of messenger ribonucleic acid (mRNA) were quantified in real-time reverse transcriptase-polymerase chain reaction assays.
In the middle cerebral artery and basilar artery from rats with induced SAH, enhanced biphasic responses to ET-1 were observed. The -log(50% effective concentration) value for the high-affinity phase was approximately 12, compared with approximately 8.5 for sham-operated animals. At a concentration of ET-1 of 10(-9) mmol/L (approximately equal to the physiological concentration of ET-1 in the plasma), submaximal contractions of 50 to 75% of the contraction obtained through stimulation with 60 mmol/L K(+) were now observed. Quantitative mRNA studies with the same arteries demonstrated significant increases in the number of copies of ET(B) receptor mRNA but not ET(A) receptor mRNA. Evidence of functional ET(B) receptors was provided in antagonist studies. The posterior communicating artery did not exhibit significant changes.
The altered receptor profile observed may represent the final stage in the series of events leading from SAH to actual spasm of the artery. The pharmacological data for the ET(B) receptor suggest complex interactions between normally present ET(A) receptors and up-regulated ET(B) receptors.
受器官培养诱导的血管内皮素（ET）受体群体变化的启发，我们研究了在大鼠蛛网膜下腔出血（SAH）模型的脑动脉中是否会发生此类变化。
通过向视交叉前池注射250微升血液诱导SAH。2天后，采集大脑中动脉、基底动脉和后交通动脉。进行体外药理学研究，并在实时逆转录聚合酶链反应测定中对信使核糖核酸（mRNA）水平进行定量。
在诱导SAH的大鼠的大脑中动脉和基底动脉中，观察到对ET-1的双相反应增强。高亲和力相的-log（50%有效浓度）值约为12，而假手术动物约为8.5。在ET-1浓度为10^(-9) mmol/L（约等于血浆中ET-1的生理浓度）时，现在观察到通过60 mmol/L K(+)刺激获得的收缩的50%至75%的次最大收缩。对相同动脉的定量mRNA研究表明，ET(B)受体mRNA的拷贝数显著增加，但ET(A)受体mRNA没有增加。拮抗剂研究提供了功能性ET(B)受体的证据。后交通动脉未表现出显著变化。
观察到的受体谱改变可能代表了从SAH到动脉实际痉挛的一系列事件的最后阶段。ET(B)受体的药理学数据表明正常存在的ET(A)受体与上调的ET(B)受体之间存在复杂的相互作用。
