Journal article
Neuronal nitric oxide synthase and N-methyl- d-aspartate neurons in experimental carbon monoxide poisoning
Toxicology and applied pharmacology, v 194(3), pp 280-295
2004
PMID: 14761684
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
We measured changes in nitric oxide (
NO) concentration in the cerebral cortex during experimental carbon monoxide (CO) poisoning and assessed the role for
N-methyl-
d-aspartate receptors (NMDARs), a glutamate receptor subtype, with progression of CO-mediated oxidative stress. Using microelectrodes,
NO concentration was found to nearly double to 280 nM due to CO exposure, and elevations in cerebral blood flow, monitored as laser Doppler flow (LDF), were found to loosely correlate with
NO concentration. Neuronal nitric oxide synthase (nNOS) activity was the cause of the
NO elevation based on the effects of specific NOS inhibitors and observations in nNOS knockout mice. Activation of nNOS was inhibited by the NMDARs inhibitor, MK 801, and by the calcium channel blocker, nimodipine, thus demonstrating a link to excitatory amino acids. Cortical cyclic GMP concentration was increased due to CO poisoning and shown to be related to
NO, versus CO, mediated guanylate cyclase activation. Elevations of
NO were inhibited when rats were infused with superoxide dismutase and in rats depleted of platelets or neutrophils. When injected with MK 801 or 7-nitroindazole, a selective nNOS inhibitor, rats did not exhibit CO-mediated nitrotyrosine formation, myeloperoxidase (MPO) elevation (indicative of neutrophil sequestration), or impaired learning. Similarly, whereas CO-poisoned wild-type mice exhibited elevations in nitrotyrosine and myeloperoxidase, these changes did not occur in nNOS knockout mice. We conclude that CO exposure initiates perivascular processes including oxidative stress that triggers activation of NMDA neuronal nNOS, and these events are necessary for the progression of CO-mediated neuropathology.
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Details
- Title
- Neuronal nitric oxide synthase and N-methyl- d-aspartate neurons in experimental carbon monoxide poisoning
- Creators
- Stephen R Thom - University of PennsylvaniaDonald Fisher - University of PennsylvaniaJie Zhang - University of PennsylvaniaVeena M Bhopale - University of PennsylvaniaBruce Cameron - University of PennsylvaniaDonald G Buerk - University of Pennsylvania
- Publication Details
- Toxicology and applied pharmacology, v 194(3), pp 280-295
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000189379100009
- Scopus ID
- 2-s2.0-0842329536
- Other Identifier
- 991019231750704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Pharmacology & Pharmacy
- Toxicology