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

J Cardiovasc Pharmacol. 2003 Sep;42(3):403-9. doi: 10.1097/00005344-200309000-00012.

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 Nomega-nitro-L-arginine-methyl-ester (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atropine / pharmacology
  • Blood Pressure / drug effects
  • Brain Ischemia / etiology
  • Brain Ischemia / prevention & control
  • Cerebrovascular Circulation / drug effects*
  • Heart Rate / drug effects
  • Kynurenine / pharmacology*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Polarography / methods
  • Rabbits

Substances

  • Kynurenine
  • Atropine
  • NG-Nitroarginine Methyl Ester