Antioxidants increase the ventilatory response to hyperoxic hypercapnia.

Abstract

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. 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. 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). 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. Antioxidants, by augmenting the tidal volume, increase the sensitivity of the ventilatory response to carbon dioxide, either during unloaded breathing or after resistive breathing.