title: Inhibition of nitric oxide synthase protects against hypoxic neuronal injury.
abstract: We investigated the action of nitric oxide in hypoxic neuronal injury, using the hippocampal slice. Inhibition of nitric oxide synthase with the competitive inhibitor, NG-monomethyl-L-arginine, provided significant protection against hypoxia for population spike, EPSP and fiber volley responses, with an EC50 of 30 microM for protection of antidromic population spike amplitude. Confirming a stereo-specific site of action, this protection was reversed by the addition of L-arginine, but not D-arginine. These results indicate that nitric oxide generation may mediate acute CA1 neuronal injury during hypoxia, and that inhibition of nitric oxide synthase may be a useful neuroprotective strategy.
authors.affiliation: Department of Neurology, UCLA School of Medicine, Sepulveda VAMC 91343.
authors.forename: R A
authors.initials: RA
authors.lastname: Wallis
authors.forename: K
authors.initials: K
authors.lastname: Panizzon
authors.forename: C G
authors.initials: CG
authors.lastname: Wasterlain
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001119:Arginase / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015687:Cell Hypoxia / Q000187:drug effects*; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007536:Isomerism; D007700:Kinetics; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019001:Nitric Oxide Synthase; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine
chemical_list: D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase