Inhibition of nitric oxide synthase protects against hypoxic neuronal injury.
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.
Wallis
R A
RA
Department of Neurology, UCLA School of Medicine, Sepulveda VAMC 91343.
Panizzon
K
K
Wasterlain
C G
CG
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
D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D001119:Arginase