Increased sensitivity to seizures in repeated exposures to hyperbaric oxygen: role of NOS activation.
Nitric oxide is involved in the mechanism of hyperbaric oxygen (HBO(2)) brain toxicity as nitric oxide synthase (NOS) inhibitors delay latent time before the onset of seizures. The purpose of this study was to investigate if seizures affect sensitivity to convulsions during subsequent exposure to HBO(2) and to determine if NOS activity and expression is changed after HBO(2) seizures. Rats were exposed to 5 atm (gauge pressure) 100% O(2) until seizures recorded by electroencephalograph (EEG) and reexposed 1, 2, or 6 days later. Latency to seizures was significantly shorter (P<0.05) in animals reexposed 1 or 2 days after the first exposure. Activity of calcium-dependent NOS activity in cortex was significantly higher 1 and 2 days after seizures compared with controls (P<0.05), while calcium-independent NOS activity was not changed during the 6-day post-seizure interval. The expression of neuronal NOS (nNOS) protein determined by Western blot was higher 1 and 2 days after seizures (P<0.05), while the expression of endothelial (eNOS) and inducible (iNOS) remained unchanged. nNOS upregulation 1 and 2 days after seizures and protection against HBO(2) seizures by nNOS-specific inhibitor 7-nitroindazole (7-NI) suggest possible involvement of NO in the mechanism of increased sensitivity to HBO(2) in reexposures.
Chavko
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Environmental Physiology Department, Naval Medical Research Center, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. chavkom@nmrc.navy.mil
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Keyser
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D000818:Animals; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000201:enzymology; D004569:Electroencephalography; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006931:Hyperbaric Oxygenation; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012016:Reference Values; D012640:Seizures / Q000175:diagnosis / Q000201:enzymology / Q000209:etiology* / Q000517:prevention & control; D013997:Time Factors
D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D002118:Calcium; C080122:7-nitroindazole