title: Hypobaric hypoxia modifies constitutive nitric oxide synthase activity and protein nitration in the rat cerebellum.
abstract: Ischemic hypoxia provokes alterations in the production system of nitric oxide in the cerebellum. We hypothesize that the nitric oxide system may undergo modifications due to hypobaric hypoxia and that may play a role in high altitude pathophysiology. Therefore, changes in the nitric oxide system of the cerebellum of rats submitted to acute hypobaric hypoxia were investigated. Adult rats were exposed for 7 h to a simulated altitude of 8235 m (27000 ft.) and then killed after 0 h or 1, 3, 5 and 10 days of reoxygenation. Nitric oxide synthase calcium-dependent and -independent activity, immunoblotting and immunohistochemistry of neuronal, endothelial, and inducible nitric oxide synthase, and nitrotyrosine were evaluated. Immunoreactivity for neuronal nitric oxide synthase slightly increased in the baskets of the Purkinje cell layer and in the granule cells, after 0 h of reoxygenation, although no changes in neuronal nitric oxide synthase immunoblotting densitometry were detected. Calcium-dependent activity significantly rose after 0 h of reoxygenation, reaching control levels in the following points, and being coincident with a peak of eNOS expression. Nitrotyrosine formation showed significant increments after 0 h and 1 day of reoxygenation. Nitrotyrosine immunoreactivity showed an intracellular location change in the neurons of the cerebellar nuclei and in addition, an appearance of nitration in the soma of the Purkinje cells was detected. No changes in inducible nitric oxide synthase activity, immunoblotting or immunohistochemistry were detected. We conclude that at least part of the nitric oxide system is involved in cerebellum responses to hypobaric hypoxia.
authors.affiliation: Department of Neuroanatomy and Cell Biology, Instituto Cajal, CSIC, Doctor Arce Av. 37, E-28002 Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Serrano
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Encinas
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salas
authors.forename: Ana Patricia
authors.initials: AP
authors.lastname: Fernández
authors.forename: Susana
authors.initials: S
authors.lastname: Castro-Blanco
authors.forename: Paula
authors.initials: P
authors.lastname: Fernández-Vizarra
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bentura
authors.forename: José
authors.initials: J
authors.lastname: Rodrigo
mesh_terms: D000531:Altitude; D000818:Animals; D002531:Cerebellum / Q000098:blood supply / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D000860:Hypoxia / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat