Effect of Systemic Administration of L-Kynurenine on Corticocerebral Blood Flow under Normal and Ischemic Conditions of the Brain in Conscious Rabbits

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.