INHIBITION OF NITRIX 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, N(G)-monomethyl-L-arginine, provided significant protection against hypoxia for population spike, EPSP and fiber volley responses, with an EC50 of 30-mu-M 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 acuteCA1 neuronal injury during hypoxia, and that inhibition of nitric oxide synthase may be a useful neuroprotective strategy.