YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
誌上シンポジウム
脳塞栓症による血管内皮細胞障害と新規血管保護薬
韓 峰福永 浩司
著者情報
ジャーナル フリー

2007 年 127 巻 4 号 p. 743-748

詳細
抄録

  Microsphere embolism-induced up-regulation of endothelial nitric oxide synthase (eNOS) in endothelial cells of brain microvessels was found after brain ischemia. The eNOS induction preceded disruption of the blood-brain barrier following ischemia. In vascular endothelial cells, microsphere embolism-induced eNOS expression was associated with protein tyrosine nitration, which is a marker of generation of peroxynitrite. To determine whether eNOS expression and protein tyrosine nitration in vascular endothelial cells mediates the blood-brain barrier disruption in the microsphere embolism brain, we tested the effect of a novel calmodulin-dependent NOS inhibitor, DY-9760e, which inhibits eNOS activity and in turn protein tyrosine nitration. Concomitant with inhibition of protein tyrosine nitration in vascular endothelial cells, DY-9760e significantly inhibited BBB disruption as assessed by Evans blue excretion. DY-9760e also inhibited cleavage of poly(ADP-ribose) polymerase as a marker of the apoptotic pathway in vascular endothelial cells. Taken together with previous evidence in which DY-9760e inhibited brain edema, microsphere embolism-induced eNOS expression in vascular endothelial cells likely mediates BBB disruption and in turn brain edema.

著者関連情報
© 2007 by the PHARMACEUTICAL SOCIETY OF JAPAN
前の記事 次の記事
feedback
Top