Brain embolism-induced injury of vascular endothelial cells and a novel vasoprotective drug

Feng Han, Kohji Fukunaga

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)743-748
Number of pages6
JournalYakugaku Zasshi
Volume127
Issue number4
DOIs
Publication statusPublished - 2007 Apr 1

Keywords

  • Blood-brain barrier
  • Calmodulin
  • Endothelial cells
  • Microsphere embolism
  • Nitric oxide synthase
  • Tyrosine nitration

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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