Linked Life Data

16581191

Source:http://linkedlifedata.com/resource/pubmed/id/16581191

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-5-29
pubmed:abstractText
Previously, we have shown that hypoxia results in increased generation of nitric oxide free radicals in the cerebral cortex of newborn piglets that may be due to up-regulation of nitric oxide synthases, neuronal nitric oxide synthase and inducible nitric oxide synthase. The present study tests the hypothesis that hypoxia results in increased expression of neuronal nitric oxide synthase and inducible nitric oxide synthase in the cerebral cortex of newborn piglets and that the increased expression is nitric oxide-mediated. Newborn piglets, 2-4 days old, were divided to normoxic (n=4), hypoxic (n=4) and hypoxic-treated with 7-nitro-indazole-sodium salt, a selective neuronal nitric oxide synthase inhibitor (hypoxic-7-nitro-indazole-sodium salt, n=6, 1 mg/kg, 60 min prior to hypoxia). Piglets were anesthetized, ventilated and exposed to an FiO2 of 0.21 or 0.07 for 60 min. Cerebral tissue hypoxia was documented biochemically by determining ATP and phosphocreatine. The expression of neuronal nitric oxide synthase and inducible nitric oxide synthase was determined by Western blot using specific antibodies for neuronal nitric oxide synthase and inducible nitric oxide synthase. Protein bands were detected by enhanced chemiluminescence, analyzed by imaging densitometry and the protein band density expressed as absorbance (OD x mm(2)). The density of neuronal nitric oxide synthase in the normoxic, hypoxic and hypoxic-7-nitro-indazole-sodium salt groups was: 41.56+/-4.27 in normoxic, 61.82+/-3.57 in hypoxic (P<0.05) and 47.80+/-1.56 in hypoxic-7-nitro-indazole-sodium salt groups (P=NS vs normoxic), respectively. Similarly, the density of inducible nitric oxide synthase in the normoxic, hypoxic and hypoxic-7-nitro-indazole-sodium salt groups was: 105.21+/-9.09, 157.71+/-13.33 (P<0.05 vx normoxic), 117.84+/-10.32 (p=NS vx normoxic), respectively. The data show that hypoxia results in increased expression of neuronal nitric oxide synthase and inducible nitric oxide synthase proteins in the cerebral cortex of newborn piglets and that the hypoxia-induced increased expression is prevented by the administration of 7-nitro-indazole-sodium salt. Furthermore, the neuronal nitric oxide synthase inhibition prevented the inducible nitric oxide synthase expression for a period of 7 days after hypoxia. Since administration of 7-nitro-indazole-sodium salt prevents nitric oxide generation by inhibiting neuronal nitric oxide synthase, we conclude that the hypoxia-induced increased expression of neuronal nitric oxide synthase and inducible nitric oxide synthase is mediated by neuronal nitric oxide synthase derived nitric oxide. We speculate that during hypoxia nitric oxide-mediated up-regulation of nitric oxide synthases will continue the perpetual cycle of nitric oxide generation-->NOS up-regulation-->nitric oxide generation resulting in hypoxic neuronal death.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
140
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
857-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16581191-Adenosine Triphosphate, pubmed-meshheading:16581191-Animals, pubmed-meshheading:16581191-Animals, Newborn, pubmed-meshheading:16581191-Cell Death, pubmed-meshheading:16581191-Cerebral Cortex, pubmed-meshheading:16581191-Cerebral Infarction, pubmed-meshheading:16581191-Disease Models, Animal, pubmed-meshheading:16581191-Enzyme Activation, pubmed-meshheading:16581191-Enzyme Inhibitors, pubmed-meshheading:16581191-Hypoxia, Brain, pubmed-meshheading:16581191-Indazoles, pubmed-meshheading:16581191-Nerve Degeneration, pubmed-meshheading:16581191-Neurons, pubmed-meshheading:16581191-Nitric Oxide, pubmed-meshheading:16581191-Nitric Oxide Synthase Type I, pubmed-meshheading:16581191-Nitric Oxide Synthase Type II, pubmed-meshheading:16581191-Phosphocreatine, pubmed-meshheading:16581191-Sus scrofa, pubmed-meshheading:16581191-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
Nitric oxide-mediated mechanism of neuronal nitric oxide synthase and inducible nitric oxide synthase expression during hypoxia in the cerebral cortex of newborn piglets.
pubmed:affiliation
Department of Pediatrics, Drexel University College of Medicine, and St. Christopher's Hospital for Children, Philadelphia, PA 19129, USA. Mishra@drexel.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural