Kwan Aij-Lie, Lin Chih-Lung, Chang Chih-Zen, Wu Shu-Chuan, Howng Shen-Long, Jeng Arco Y
Department of Neurosurgery, Kaohsiung Medical University, Kaohsiung, Taiwan.
Neuroreport. 2002 Feb 11;13(2):197-9. doi: 10.1097/00001756-200202110-00005.
CGS 26303, a dual inhibitor of endothelin-converting enzyme-1 (ECE-1) and neutral endopeptidase 24.11, was previously shown to prevent and reverse vasospasm in an experimental model of subarachnoid hemorrhage (SAH). However, reversal of the vasospastic response was not very efficacious. This study was designed to examine the effects of a highly selective ECE-1 inhibitor, CGS 35066, on SAH-induced cerbrovasospasm. Experimental SAH was induced in New Zealand white rabbits by injecting autogenous blood into cisterna magna and CGS 35066 was injected i.v. twice daily, either at 1 h (prevention protocol) or 24 h (reversal protocol) after SAH. Treatment with CGS 35066 significantly attenuated basilar arterial narrowing at a dose of 1 mg/kg in both protocols. These findings provide support for the use of selective ECE-1 inhibitors for the treatment of SAH-induced vasospasm even after the process of arterial narrowing has begun.
CGS 26303是一种内皮素转化酶-1（ECE-1）和中性内肽酶24.11的双重抑制剂，先前已证实在蛛网膜下腔出血（SAH）实验模型中可预防和逆转血管痉挛。然而，血管痉挛反应的逆转效果不是很显著。本研究旨在考察高选择性ECE-1抑制剂CGS 35066对SAH诱导的脑血管痉挛的影响。通过向新西兰白兔的大池内注入自体血诱导实验性SAH，并在SAH后1小时（预防方案）或24小时（逆转方案）每天静脉注射两次CGS 35066。在两个方案中，CGS 35066以1mg/kg的剂量治疗均显著减轻了基底动脉狭窄。这些发现为即使在动脉狭窄过程已经开始后，使用选择性ECE-1抑制剂治疗SAH诱导的血管痉挛提供了支持。
