Kynurenic acid attenuates NMDA-induced pial arteriolar dilation in newborn pigs

Ferenc Bari, Krisztina Nagy, Paolo Guidetti, Robert Schwarcz, David W. Busija, Ferenc Domoki

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The excitatory amino acid glutamate is a potent vasodilator in the central nervous system. Glutamate-induced vasodilation is mediated primarily by N-methyl-d-aspartate (NMDA) and AMPA/kainate (KAIN) receptors. We have now tested whether two metabolites of the kynurenine pathway of tryptophan degradation acting at the NMDA receptor, the antagonist kynurenic acid (KYNA) and the agonist quinolinic acid (QUIN), are capable of modulating the dilation of pial arterioles. The closed cranial window technique was used, and changes in vessel diameter (∼100 μm) were analyzed in anesthetized newborn piglets. Topical application of NMDA (10-4 M) or KAIN (5 × 10 -5 M) resulted in marked vasodilation (44 ± 5% and 39 ± 4%, respectively). Neither KYNA nor QUIN (both at 10-5 to 10 -3 M) affected the vessel diameter when applied alone. Co-application of KYNA dose-dependently reduced the vasodilation caused by 10-4 M NMDA and also attenuated the KAIN-induced response. Ten minutes of global cerebral ischemia did not modify the interaction between KAIN and KYNA. In contrast, KYNA did not affect vasodilation to hypercapnia, elicited by the inhalation of 10% CO2. Moreover, endogenous levels of KYNA and QUIN in the cerebral cortex, hippocampus and thalamus were found to be essentially unchanged during the early reperfusion period (0.5-2 h) following an episode of cerebral ischemia. Our data are relevant for the use of drugs that target the kynurenine pathway for therapeutic interventions in cerebrovascular diseases.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalBrain research
Volume1069
Issue number1
DOIs
Publication statusPublished - Jan 19 2006

Keywords

  • Cranial window
  • Global cerebral ischemia
  • Hypercapnia
  • Kainate
  • Quinolinic acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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