Neurotoxic effects of sodium nitroprusside in rat hippocampal slices.
To investigate the possible role of nitric oxide (NO) in n-methyl-D-aspartate (NMDA)-induced neurotoxicity we examined the effects of sodium nitroprusside (SNP) in rat hippocampal slices. Incubation with 3 mM SNP for up to 2 h produced neuronal damage characterized by "nuclear ballooning" in CA3 and CA1 pyramidal neurons and interneurons. The nuclear ballooning was not blocked by lowering the external calcium concentration or coincubation with MK-801 and/or 6,7-dinitro-quinoxaline-2,3-dione. Two lines of evidence suggest that the SNP neurotoxicity is not mediated by NO. First, inactivation of SNP by UV light failed to prevent the nuclear ballooning. Second, the toxicity was not attenuated by coadministration of hemoglobin. Although cyanide can be released from SNP, potassium cyanide did not mimic the nuclear ballooning. In electrophysiological experiments, 100 microM SNP irreversibly diminished the CA1 population spike amplitude while having less effect on the field excitatory postsynaptic potential. The effect of SNP on population spikes was inhibited by hemoglobin and was not mimicked by light-inactivated SNP. These results suggest that active SNP and light-treated SNP have different effects on hippocampal neurons and that SNP induces damage that differs from that produced by NMDA or cyanide.
Izumi
Y
Y
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63100.
Benz
A M
AM
Clifford
D B
DB
Zorumski
C F
CF
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D016202:N-Methylaspartate / Q000633:toxicity; D009498:Neurotoxins / Q000494:pharmacology*; D009599:Nitroprusside / Q000633:toxicity*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012966:Sodium Cyanide / Q000633:toxicity
D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D009599:Nitroprusside; D016202:N-Methylaspartate; D012966:Sodium Cyanide