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Effect of 7-Nitroindazole Sodium on the Cellular Distribution of Neuronal Nitric Oxide Synthase in the Cerebral Cortex of Hypoxic Newborn Piglets

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Abstract

Cerebral hypoxia results in generation of nitric oxide (NO) free radicals by Ca++-dependent activation of neuronal nitric oxide synthase (nNOS). The present study tests the hypothesis that the hypoxia-induced increased expression of nNOS in cortical neurons is mediated by NO. To test this hypothesis the cellular distribution of nNOS was determined immunohistochemically in the cerebral cortex of hypoxic newborn piglets with and without prior exposure to the selective nNOS inhibitor 7-nitroindazole sodium (7-NINA). Studies were conducted in newborn piglets, divided into normoxic (n = 6), normoxic treated with 7-NINA (n = 6), hypoxic (n = 6) and hypoxic pretreated with 7-NINA (n = 6). Hypoxia was induced by lowering the FiO2 to 0.05–0.07 for 1 h. Cerebral tissue hypoxia was documented by decrease of ATP and phosphocreatine levels in both the hypoxic and 7-NINA pretreated hypoxic groups (P < 0.01). An increase in the number of nNOS immunoreactive neurons was observed in the frontal and parietal cortex of the hypoxic as compared to the normoxic groups (P < 0.05) which was attenuated by pretreatment with 7-NINA (P < 0.05 versus hypoxic). 7-NINA affected neither the cerebral energy metabolism nor the cellular distribution of nNOS in the cerebral cortex of normoxic animals. We conclude that nNOS expression in cortical neurons of hypoxic newborn piglets is NO-mediated. We speculate that nNOS inhibition by 7-NINA will protect against hypoxia-induced NO-mediated neuronal death.

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Abbreviations

7-NINA:

7 nitroindazole sodium

NNLA:

N-nitro-l-arginine

NO:

nitric oxide

NOS:

nitric oxide synthase

INOS:

inducible nitric oxide synthase

nNOS:

neuronal nitric oxide synthase

PCr:

phosphocreatine

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Acknowledgements

The study was supported by the National Institutes of Health grants NIH-HD-38079 and NIH-HD-20337.

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Authors and Affiliations

  1. Department of Pediatrics, Drexel University College of Medicine and St. Christopher’s Hospital for Children, Philadelphia, PA, USA

    Christos D. Katsetos, Nehal A. Parikh, Karen I. Fritz, Agustin Legido, Maria Delivoria-Papadopoulos & Om P. Mishra

  2. Department of Pathology and Laboratory Medicine, St. Christopher’s Hospital for Children, Philadelphia, PA, USA

    Christos D. Katsetos

  3. Section of Neurology, St. Christopher’s Hospital for Children, Erie Avenue at Front Street, Philadelphia, PA, 19134, USA

    Christos D. Katsetos

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  1. Christos D. Katsetos
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  2. Nehal A. Parikh
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  3. Karen I. Fritz
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  4. Agustin Legido
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  5. Maria Delivoria-Papadopoulos
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  6. Om P. Mishra
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Correspondence to Christos D. Katsetos.

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Katsetos, C.D., Parikh, N.A., Fritz, K.I. et al. Effect of 7-Nitroindazole Sodium on the Cellular Distribution of Neuronal Nitric Oxide Synthase in the Cerebral Cortex of Hypoxic Newborn Piglets. Neurochem Res 31, 899–906 (2006). https://doi.org/10.1007/s11064-006-9094-y

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