Immunohistochemical study of endothelin converting enzyme inhibitor [D-Val22] big ET-1(16-38) for the prevention and treatment of cerebral vasospasm

    ZHAO Zhenª²Wei,GAO Guoª²Dong, ZHAO Jiª²Pei,QIN Huaiª²Zhou, DENG Jianª²Ping, CHEN Ling, WEI Deª²Lai

    1Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University,Xian 710038, China, 2Department of Neurosurgery, People¬ðs Hospital, Jishan County of Shanxi Province, Jishan 043200, China

    ¡¾Abstract¡¿AIM£º To investigate the function of endothelinª²1 (ETª²1) in the cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH), the effects of [Dª²Val22] big ETª²1 (16ª²38), an endothelin converting enzyme inhibitor, on the expression of ETª²1 in the wall of basilar artery and the differences of these effects by different ways and timing of injection. METHODS: CVS models were developed by injecting arterial blood twice through the citerna magna 48 hours apart. Thirtyª²six rabbits were equally assigned to six groups: control group, SAH group, prevention group with citerna magna injection, prevention group with intravenous injection, treatment group with citerna magna injection, and treatment group with intravenous injection group. All animals were killed for perfusionª²fixation on day 7. The basilar arteries and some brain tissue were removed for immunohistochemical studies. RESULTS: The immunohistochemical study on SAH day 7 found that in control group, the basilar arteries showed scattered irregular positive staining, and in SAH group, severe positive staining was found in EC, SMC and adventitia, especially in EC. In the other four groups, EC, SMC and adventitia showed slightly immunohistochemical staining. But there was no positive staining in brain cells adjacent to basilar artery. CONCLUSION: This study demonstrates that Big ETª²1(16ª²38) markedly inhibits immunological expression of ETª²1 in basilar arteries, which not only effectively prevents CVS, but also reverses CVS via the cisterna magna or intravenously. Our study indirectly proves that ETª²1 is a major pathogenic factor of CVS. ......