Chemoreflex control of breathing during wakefulness in healthy men and women

Dennis Jensen, Larry A. Wolfe, Denis E. O'Donnell, Gregory A. L. Davies
2005 Journal of applied physiology  
Chemoreflex control of breathing during wakefulness in healthy men and women. This study used a modified CO2 rebreathing procedure to examine the effect of gender on the chemoreflex control of breathing during wakefulness in healthy men (n ϭ 14) and women (n ϭ 14). Women were tested in the follicular phase of the menstrual cycle. During rebreathing trials, subjects hyperventilated to reduce the partial pressure of end-tidal CO2 (PETCO 2 ) below 25 Torr and were then switched to a rebreathing
more » ... to a rebreathing bag containing a normocapnic hypoxic or hyperoxic gas mixture. During the trial, PETCO 2 increased, while O2 was maintained at a constant level. The point at which ventilation began to rise as PETCO 2 increased was identified as the ventilatory recruitment threshold (VRT). Ventilation below the VRT was measured, and the slope of the ventilatory response above the VRT was determined. Gender had no effect on the hyperoxic or hypoxic VRT for CO2. Central chemoreflex sensitivity was significantly greater in men than women but not after correction for forced vital capacity. Measures of peripheral chemoreflex sensitivity were similar between genders. However, the slope of the tidal volume (VT) response to hyperoxic and hypoxic CO2 rebreathing (corrected and uncorrected) was greater in men than women, respectively. We conclude that central chemoreflex sensitivity is greater in men compared with women as reflected by differences in ventilatory (uncorrected) and VT (corrected and uncorrected) responses to CO2. However, gender has no significant effect on the central chemoreflex VRT for CO 2. The peripheral chemoreflex control of breathing during wakefulness is similar between men and women. hypoxia; chemoreflex sensitivity; ventilatory recruitment threshold; sleep-disordered breathing OVARIAN AND TESTICULAR HORMONES influence the control of breathing via their effects on both central and peripheral chemoreflexes (2, 33). Progesterone increases central and peripheral chemosensitivity to hypercapnia and hypoxia (2, 33). This effect is potentiated by estrogen (2, 33). In addition, testosterone increases peripheral chemoreflex sensitivity to hypoxia (2, 17, 33), but its effect on central chemoresponsiveness remains unclear (2, 33). Given the effects of reproductive hormones on ventilatory control as well as gender differences in endocrine status, it is reasonable to expect that central and/or peripheral chemoreflex control characteristics may differ between healthy men and women during wakefulness. Current evidence suggests that the apneic threshold and sensitivity of the ventilatory response to CO 2 , mediated by the central chemoreflex, is greater in men than women (20, 26, 35, 37) , regardless of menstrual cycle status (20, 33, 35) . Some studies have shown that the ventilatory response to hypoxia, mediated by the peripheral chemoreflex, is greater in men than women (20, 32, 33), whereas others have reported the opposite result (1). However, others have found that gender has no effect on either central (1, 13, 18, 26, 30, 34) or peripheral (13, 26, 27, 32, 34) chemoreflex sensitivity. Divergent results from previous investigations may be due to different experimental designs. Some studies did not control for menstrual cycle status of female subjects (20, 21, 28, 30, 32, 34) , whereas others made comparisons between men and women in the luteal phase (37) and follicular phase (FP) (1, 13, 26, 27) of the menstrual cycle. Also, some studies have not considered oral contraceptive use among female volunteers (21, 28, 30) or gender differences in body size and/or lung functional indexes (20, 26, 28) . Recent epidemiological studies (4, 36) have demonstrated that the prevalence of sleep-disordered breathing (SDB), a condition of repeated apneas, hypopneas, and breathing oscillations, is two to three times greater in men than women (4, 36). Differences in the central and/or peripheral chemoreflex control of breathing during wakefulness may reflect a similar difference during sleep that could contribute to the high male prevalence of SDB (12, 37). This study investigated the effect of gender on the ventilatory recruitment threshold (VRT) for CO 2 and the ventilatory response below (i.e., behavioral drives) and above (i.e., chemoreflex sensitivity) this threshold while maintaining constant backgrounds of hyperoxia and hypoxia, respectively. We hypothesized that neither the hyperoxic nor hypoxic VRT for CO 2 would differ between men and women. In addition, we hypothesized that the ventilatory response to CO 2 below and above this threshold would be greater in men than women, independent of the level of O 2 . METHODS Subjects. Healthy, nonsmoking, normally active men (n ϭ 14) and women (n ϭ 14), aged 20 -35 yr, were recruited at Queen's University through posted announcements and flyers. Subjects had no history of cardiorespiratory disease, nor were they born at or recently returned from high altitude. None was taking medications that affect ventilatory control. Female subjects had regular menstrual cycles, as verified by questionnaire, and had not used oral contraceptives for 6 mo before experimental testing. Before study entry, subjects attended an information session to familiarize them with the laboratory and study procedures. All subjects completed the revised Physical Activity Readiness Questionnaire (available online at to ensure that there were no contraindications to participation. Demographic information, including age, occupation, and occupational and recreational physical activity levels, were assessed by questionnaire. To evaluate menstrual
doi:10.1152/japplphysiol.01208.2003 pmid:15557008 fatcat:2helresajbf57g3z5xdllm5f4i