Effect of systemic administration of L-kynurenine on corticocerebral blood flow under normal and ischemic conditions of the brain in conscious rabbits

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Abstract

Kynurenic acid, the only known endogenous antagonist of the excitatory amino acid receptors, exerts neuroprotective effect in focal cerebral ischemia. Kynurenic acid poorly while its bioprecursor, L-kynurenine (L-KYN) completely crosses the blood-brain barrier. The aim of our study was to investigate the effect of intravenous L-KYN (0.3, 1, and 3 mg/kg) on the normal and the unilateral carotid artery occlusion induced ischemic corticocerebral blood flow (cCBF) measured by hydrogen polarography in conscious rabbits. Administration of L-KYN produced a significant increase in the normal cCBF; the peak values were recorded at the dose of 1 mg/kg (187% at 120 and 150 mins. respectively). The cCBF-improving effect of L-KYN was immediate and highly pronounced also in rabbits with carotid occlusion (peak value was 192% at 120 mins. at the dose of 1 mg/kg). Pretreatment with either atropine or Nω -nitro-L-arginine-methylester (L-NAME) prevented the L-KYN induced enhancement of the normal and the ischemic cCBF alike. It is suggested that the cCBF-increasing effect of L-KYN might be mediated by activation of cholinergic and nitric oxide pathways.

Original languageEnglish
Pages (from-to)403-409
Number of pages7
JournalJournal of cardiovascular pharmacology
Volume42
Issue number3
DOIs
Publication statusPublished - Sep 1 2003

Keywords

  • Conscious rabbits
  • Corticocerebral blood flow
  • Hydrogen polarography
  • L-kynurenine

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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