title: Antioxidants increase the ventilatory response to hyperoxic hypercapnia.
abstract: BACKGROUND
  The mechanisms by which chemoreceptors process carbon dioxide stimuli are poorly understood. Recent in vitro studies suggest a role of reactive oxygen species in central carbon dioxide chemoreception.
  
  
  OBJECTIVE
  We tested the hypothesis that antioxidant treatment modulates the ventilatory response to carbon dioxide in healthy humans, either during unloaded breathing or after strenuous resistive breathing.
  
  
  METHODS
  In the first experiment of this randomized, double-blind, placebo-controlled study, 14 healthy males completed hyperoxic carbon dioxide rebreathing, received either antioxidants (vitamins E, A, and C for 2 mo, allopurinol for 15 d, and N-acetylcysteine for 3 d) (n = 7) or placebo (n = 7), and repeated rebreathing 3 mo later. In the second experiment, 18 healthy males completed a series of rebreathing tests before and after strenuous resistive breathing. Subjects repeated the same protocol 3 mo later, after they had received antioxidants (n = 9) or placebo (n = 9).
  
  
  RESULTS
  After antioxidants, the sensitivity of the ventilatory (minute ventilation) response to carbon dioxide increased (mean [+/- SEM], 3.2 +/- 0.5 vs. 1.7 +/- 0.4 L/min/mm Hg; p < 0.001). Antioxidants also increased the sensitivity to carbon dioxide before and at 5, 30, and 120 min after resistive breathing (p = 0.01). This effect was entirely due to increased tidal volume. Antioxidants did not influence the breathing pattern during resting breathing or the rapid shallow breathing response to carbon dioxide at 5 min after resistive breathing.
  
  
  CONCLUSIONS
  Antioxidants, by augmenting the tidal volume, increase the sensitivity of the ventilatory response to carbon dioxide, either during unloaded breathing or after resistive breathing.
authors.affiliation: Medical School of Athens University, Department of Critical Care and Pulmonary Services, Evangelismos Hospital, 45-47 Ipsilandou St., GR 106 75 Athens, Greece. szakynthinos@yahoo.com
authors.forename: Spyros
authors.initials: S
authors.lastname: Zakynthinos
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Katsaounou
authors.forename: Maria-Helena
authors.initials: MH
authors.lastname: Karatza
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
authors.forename: Theodoros
authors.initials: T
authors.lastname: Vassilakopoulos
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000819:agonists* / Q000494:pharmacology; D006801:Humans; D006935:Hypercapnia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010919:Placebos; D012123:Pulmonary Ventilation / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D000975:Antioxidants; D010919:Placebos; D002245:Carbon Dioxide