Vatter Hartmut, Konczalla Jürgen, Seifert Volker
Department of Neurosurgery, Center of Clinical Neurosciences, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
Acta Neurochir Suppl. 2011;110(Pt 1):177-80. doi: 10.1007/978-3-7091-0353-1_31.
The central role of Endothelin (ET) in the development of cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is supported by several investigations. These investigations provided, furthermore, that changes of the ET-receptor expression and function in the wall of the cerebral arteries are a considerable factor for the development of CVS. The biological activity of ET-1 is mediated by two receptor subtypes, named ET(A) and ET(B). Under physiological conditions the dominant vasocontractile effect of ET-1 is mediated by ET(A)-receptors on smooth muscle cells (SMC), which is attenuated by an ET(B)-receptor dependent release of nitric oxide (NO) from endothelial cells (EC). In the physiological cerebrovasculature ECs express exclusively ET(B)- and SMCs only ET(A)-receptors. In case of CVS an increased expression of the ET(B)-receptor could be detected in cerebral vessels. However, the loss of the vasodilative and the missing of a vasocontractile ET(B)-receptor mediated effect was demonstrated. Therefore, any ET(B)-receptor mediated vasoactivity seems to be lost in case of CVS and the biological impact of the increased expression remains unclear so far. The ET(A)-receptor expression seems to be not increased during the development of CVS. Therefore, the proven increase of the ET-dependent vasocontractility seems to be rather by the loss of the ET(B)-receptor mediated effect than by an increased ET(A)-receptor activity. In spite of the more significant changes of the ET(B)-receptor expression the pathophysiological effect of ET, namely the vasoconstriction, seems to be exclusively mediated by the ET(A)-receptor. Therefore, tailored approaches for the treatment of CVS remain to be ET(A)-receptor selective antagonists.
多项研究支持内皮素（ET）在蛛网膜下腔出血（SAH）后脑血管痉挛（CVS）发生发展中的核心作用。此外，这些研究表明，脑动脉壁中ET受体表达和功能的变化是CVS发生发展的一个重要因素。ET-1的生物活性由两种受体亚型介导，即ET(A)和ET(B)。在生理条件下，ET-1的主要血管收缩作用由平滑肌细胞（SMC）上的ET(A)受体介导，而内皮细胞（EC）通过ET(B)受体依赖性释放一氧化氮（NO）来减弱这种作用。在生理性脑血管系统中，EC仅表达ET(B)受体，而SMC仅表达ET(A)受体。在CVS情况下，可检测到脑血管中ET(B)受体表达增加。然而，已证实存在血管舒张功能丧失以及ET(B)受体介导的血管收缩作用缺失。因此，在CVS情况下，任何ET(B)受体介导的血管活性似乎都已丧失，且ET(B)受体表达增加的生物学影响至今仍不清楚。在CVS发生发展过程中，ET(A)受体表达似乎并未增加。因此，已证实的ET依赖性血管收缩性增加似乎更多是由于ET(B)受体介导作用的丧失，而非ET(A)受体活性增加。尽管ET(B)受体表达变化更为显著，但ET的病理生理效应，即血管收缩，似乎仅由ET(A)受体介导。因此，治疗CVS的针对性方法仍为ET(A)受体选择性拮抗剂。
