N(omega)-nitro-L-arginine methyl ester protects retinal neurons against N-methyl-D-aspartate-induced neurotoxicity in vivo.
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.
Morizane
C
C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Adachi
K
K
Furutani
I
I
Fujita
Y
Y
Akaike
A
A
Kashii
S
S
Honda
Y
Y
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000633:toxicity; D002452:Cell Count / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000633:toxicity*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013237:Stereoisomerism; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester