ELEVATED TISSUE ENDOTHELIN CONTENT DURING FOCAL CEREBRAL-ISCHEMIA IN THE RAT

To study the involvement of endogenous endothelin (ET) in the developm ent of cerebral ischemia, we measured by radioimmunoassay brain tissue content of immunoreactive (ir)-ET-1 in a model of focal cerebral isch emia in the rat. Permanent occlusion of the middle cerebral artery (OM CA) was accompanied after 24 h by a progressive but marked elevation o f ir-ET-1 in the ipsilateral compared with the contralateral hemispher e (119% after 24 h; 184% after 48 h and 459% after 72 h). The pial ves sels 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 follo wed by recirculation led to a slight increase of ir-ET-1, which also a ppeared after 24 h of recirculation. This study demonstrates that duri ng permanent OMCA, the tissue content of ir-ET-1 markedly and progress ively increases, whereas less severe ischemia (transient) is accompani ed 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.