Effects of activation of glutamate receptors on neurons and blood vessels

David W. Busija, Ferenc Domoki, Ferenc Bari, Thomas M. Louis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Glutamate dilates pial arterioles in piglets via activation of N-methyl-D-aspartate (NMDA) receptors and increases cortical glucose utilization. Administration of NMDA, the chemical compound which was used to characterize this glutamate receptor subtype, dilates cerebral arteries via activation of nitric oxide synthase (NOS) in neurons and subsequent actions of nitric oxide (NO) on vascular smooth muscle. Thus, administration of inhibitors of NOS attenuates NMDA-induced arteriolar dilation, while inhibitors of cyclooxygenase and cytochrome P-450 epoxygenase do not alter the vascular response. Additionally, inhibition of adenosine receptors and endothelial “stunning” do not alter arteriolar dilation to NMDA. Finally, NO metabolites accumulate on the cortical surface following NMDA application. We conclude that NMDA-induced arteriolar dilation is via direct actions on smooth muscle of NO synthesized and released by cortical neurons. NMDA-induced dilator responses are severely restricted after ischemia-reperfusion. Previous studies have shown that potassium channel activators given prior to ischemia preserve responses after ischemia. However, intracellular localization of this effect is unclear. We provide evidence to indicate that activation of KATP on mitochondria by diazoxide is able to provide neuroprotection against ischemic stress, probably by restricting calcium entry into mitochondria. Use of selective activators of KATP on mitochondria could be a new therapeutic approach to protect the brain against ischemic stress.

Original languageEnglish
Pages (from-to)305-312
Number of pages8
JournalInternational Congress Series
Volume1235
Issue numberC
DOIs
Publication statusPublished - Jul 1 2002

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Keywords

  • Diazoxide
  • Endothelium
  • Ischemia
  • Mitochondria
  • N-methyl-D-aspartate
  • Nitric oxide
  • Potassium channels

ASJC Scopus subject areas

  • Medicine(all)

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