Contribution of cytochrome P450 products, EETs & 20HETE, on cerebral vasospasm

我们研制了一套可以测量大鼠软脑膜动脉内径变化和脑血流量变化的系统。应用该系统，我们发现蛛网膜下腔出血(SAH)后脑血流量和直径的急性下降可被20-HETE的抑制剂17-ODYA所阻止。我们还发现，SAH后20HETE的浓度增加，这种增加的20-HETE水平被抑制剂减弱。此外，如果我们同时阻断20-HETE的产生和另一种抑制剂增加EETS的水平，我们可以成功地逆转脑血流量的急剧下降。因此，我们的研究表明，SAH后20-HETE的产生和EETS水平的下降可能是导致脑血流量急剧下降(急性脑血管痉挛)的原因之一。此外，抑制20-HETE的产生和给予EETs可能为我们提供SAH后的治疗启示。

We developed the system in which we could measure changes of pial artery diameter, and changes in cerebral blood fow in rats. By using this system, we found that acute fall in cerebral blood flow and diameter after subarachnoid hemorrhage (SAH) was prevented by the inhibitor of 20-HETE, 17-ODYA. We also found that the concentration of 20HETE was increased after SAH, and this increased level of 20-HETE was attenuated by the inhibitor. Furthermore, if we simultaneously block 20-HETE production and increased EETs levels by the another inhibitor, we could successfully reverse the acute fall of cerebral blood flow.Therefore, from our study, it is suggested that the production of 20-HETE and may be the fall in EETs levels after SAH contributes to the acute fall in cerebral blood flow (acute cerebral vasospasm). Further, the inhibition of 20-HETE production and administration of EETS may give us therapeutic insights after SAH.