N(omega)-nitro-L-arginine methyl ester protects retinal neurons against N-methyl-D-aspartate-induced neurotoxicity in vivo

Eur J Pharmacol. 1997 Jun 5;328(1):45-9. doi: 10.1016/s0014-2999(97)83026-9.

Abstract

We investigated whether the inhibition of nitric oxide (NO) synthesis with N(omega)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, affects N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina in vivo. A single intravitreal injection of NMDA damaged the ganglion cell layer and the inner plexiform layer without affecting the other retinal layers 7 days after injection. Intravitreal injection of (5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5, 10-imine hydrogen maleate (MK-801) with NMDA significantly reduced NMDA-induced degeneration of the retina. NMDA-induced degeneration was also prevented by intravitreal injection of L-NAME but not of D-NAME. The protective effect of L-NAME was antagonized by L-arginine. These results suggest that NO plays an important role in NMDA-induced excitotoxic degeneration in the retina.

MeSH terms

  • Animals
  • Arginine / administration & dosage
  • Arginine / toxicity
  • Cell Count / drug effects
  • Dizocilpine Maleate / administration & dosage
  • Dizocilpine Maleate / pharmacology
  • Drug Interactions
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Excitatory Amino Acid Agonists / administration & dosage
  • Excitatory Amino Acid Agonists / toxicity*
  • Excitatory Amino Acid Antagonists / administration & dosage
  • Excitatory Amino Acid Antagonists / pharmacology
  • Male
  • N-Methylaspartate / administration & dosage
  • N-Methylaspartate / toxicity*
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Neurons / cytology
  • Neurons / drug effects*
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Rats
  • Rats, Sprague-Dawley
  • Retina / cytology
  • Retina / drug effects*
  • Retina / pathology
  • Stereoisomerism
  • Vitreous Body / drug effects
  • Vitreous Body / metabolism

Substances

  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • N-Methylaspartate
  • Dizocilpine Maleate
  • Arginine
  • Nitric Oxide Synthase
  • NG-Nitroarginine Methyl Ester