Viossat I, Duverger D, Chapelat M, Pirotzky E, Chabrier P E, Braquet P
Institut Henri Beaufour, Les Ulis, France.
J Cardiovasc Pharmacol. 1993;22 Suppl 8:S306-9. doi: 10.1097/00005344-199322008-00080.
To study the involvement of endogenous endothelin (ET) in the development of cerebral ischemia, we measured by radioimmunoassay brain tissue content of immunoreactive (ir)-ET-1 in a model of focal cerebral ischemia in the rat. Permanent occlusion of the middle cerebral artery (OMCA) was accompanied after 24 h by a progressive but marked elevation of ir-ET-1 in the ipsilateral compared with the contralateral hemisphere (119% after 24 h; 184% after 48 h and 459% after 72 h). The pial vessels and the arteries of the circle of Willis did not respond with ir-ET-1 production. The increase in ir-ET-1 content in tissues was first observed in the caudate nucleus (after 24 h) and later in the cortex (after 48 h), which was more variably injured. Transient ischemia followed by recirculation led to a slight increase of ir-ET-1, which also appeared after 24 h of recirculation. This study demonstrates that during permanent OMCA, the tissue content of ir-ET-1 markedly and progressively increases, whereas less severe ischemia (transient) is accompanied by a modest elevation of ir-ET-1 levels. These results suggest that endogenous ir-ET-1 production is involved in the development and the severity of ischemic injury.
为研究内源性内皮素(ET)在脑缺血发展过程中的作用,我们采用放射免疫分析法测定了大鼠局灶性脑缺血模型中免疫反应性(ir)-ET-1的脑组织含量。大脑中动脉永久性闭塞(OMCA)24小时后,同侧半球ir-ET-1较对侧半球逐渐且显著升高(24小时后升高119%;48小时后升高184%,72小时后升高459%)。软脑膜血管和 Willis 环的动脉未出现ir-ET-1生成反应。组织中ir-ET-1含量的增加首先在尾状核中观察到(24小时后),随后在皮层中观察到(48小时后),皮层受损程度变化更大。短暂缺血后再灌注导致ir-ET-1略有增加,再灌注24小时后也出现这种情况。本研究表明,在永久性OMCA期间,ir-ET-1的组织含量显著且逐渐增加,而较轻的缺血(短暂性)则伴随着ir-ET-1水平的适度升高。这些结果表明,内源性ir-ET-1的产生与缺血性损伤的发展和严重程度有关。