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Free Radical Production Is Increased During Hyperoxia And Exacerbated By Hypercapnic Acidosis (HA) In CO 2 ‐Chemosensitive Caudal Solitary Complex (cSC) Neurons In Rat Medullary Slices
Author(s) -
Ciarlone Geoffrey,
Dean Jay
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.678.12
Subject(s) - hyperoxia , chemistry , nitric oxide , superoxide , anesthesia , endocrinology , oxygen , biology , biochemistry , medicine , organic chemistry , enzyme
CNS O 2 toxicity (CNS‐OT) seizures are the limiting factor when breathing hyperbaric O 2 in diving & submarine medicine. O 2 ‐induced seizures are the result of oxidative and nitrosative stress that lead to CNS hyperexcitability. The risk for CNS‐OT increases during CO 2 retention. The cSC is an important cardiorespiratory integrative center that is stimulated during both HA & hyperoxia. The stimulatory effects of O 2 & CO 2 on cellular excitability suggests these molecules modulate one another in the CNS‐OT mechanism. We have tested the following hypotheses in rat brain slices: 1) hyperoxia (95%O 2 ) increases the production of reactive O 2 & N 2 species (RO/NS) in cSC cells (control O 2 , 40%), and 2) addition of HA exacerbates the rate of RO/NS production. We also investigated the effects of CO 2 ‐anesthesia on RO/NS production during subsequent administration of HA & hyperoxia. Fluorescence microscopy was used to measure the production rates of superoxide (˙O 2 ‐ ), nitric oxide (˙NO), and an aggregate pool of RO/NS (ONOO ‐ , ˙NO 2 ,˙CO 3 ‐ ) as the slope of fluorescence intensity (ΔFI/min). Results show the ΔFI/min of ⋅O 2 ‐ and ⋅NO increased during hyperoxia, but were only seen in the presence of NOS and SOD inhibitors or SOD mimetics, respectively. Addition of HA increased the ΔFI/min of the aggregate pool, but only during hyperoxia. The effects of HA during hyperoxia are greater when CO 2 anesthesia is not used prior to tissue harvesting. We conclude that 1) hyperoxia produces an enhanced redox and nitrosative environment for cSC neurons, 2) HA exacerbates downstream RO/NS production in an O 2 ‐dependent manner, and 3) use of CO 2 anesthesia before euthanasia may blunt the effects of HA. ONR