Antioxidants increase the ventilatory response to hyperoxic hypercapnia

RATIONALE: 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. OBJECTIVES: 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). MAIN 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.