Ventilatory Response Arising from the Interaction between the Peripheral Chemoreflex and the Muscle Mechanoreflex in Healthy Humans

Abstract

The control of ventilation is mediated by humoral and neural mechanisms. Altogether these mechanisms function redundantly, which, perhaps, is mediated in part by hyperadditive interactions of neural origin (i.e., the effect produced by activation of two reflexes is greater than the activation of each reflex in isolation). In this context, the peripheral chemoreflex control of ventilation is potentiated during exercise, as hypoxia‐induced increase and hyperoxia‐induced decrease in ventilation are greater during exercise than at rest, even at low‐intensity exercise. We thus hypothesized that the peripheral chemoreflex and the activation of mechanical afferents in skeletal muscles (i.e., mechanoreflex) could interact in a hyperadditive fashion for the regulation of ventilation in humans. To test this hypothesis, six young healthy men inhaled, randomly, in separate visits, either 1) 12% of O2 to stimulate the peripheral chemoreflex (i.e., hypoxia), 2) 100% of O2 to inhibit the peripheral chemoreflex (i.e., hyperoxia), or 3) 21% of O2 as control (i.e., normoxia). Subjects were blinded about the O2 concentration. Isocapnia was obtained via a rebreathing circuit. Administration of gases lasted ~2–3 min. Within this period, subjects either remained at rest or the mechanoreflex was activated, in random order, after the O2 levels had been raised (above 250 mmHg) or lowered (below 60 mmHg) versus normoxia. The mechanoreflex was activated via passive knee flexion and extension of the non‐dominant limb, at ~1 Hz, for 30 s, using an isokinetic dynamometer. Torque and muscle electrical activity were measured to confirm the absence of active contractions. Each procedure was repeated at least four times. Data were interpolated and time‐aligned, and then, analyzed as 30‐s averages that represented four periods: 1) baseline, 2) pre‐movement or equivalent resting period, 3) movement or equivalent resting period, 4) and post‐movement or equivalent resting period. The results showed that hypoxia increased ventilation, whereas hyperoxia decreased ventilation, compared with normoxia, both at rest and during passive limb movement. Of note, the hypoxia‐induced increase in ventilation was greater during passive limb movement (delta: 3.1 ± 1.8 L/min, mean ± SEM) than at rest (delta: 1.4 ± 1.5 L/min, P = 0.04). On the other hand, the hyperoxia‐induced decrease in ventilation was similar between passive limb movement (delta: −0.7 ± 1.2 L/min) and rest (delta: −1.0 ± 1.7 L/min, P = 0.72). Therefore, collectively, the results suggest that the peripheral chemoreflex and the mechanoreflex interact in a hyperadditive fashion for the regulation of ventilation during hypoxia in healthy young men, which, consequently, may contribute for the greater hypoxia‐mediated increase in ventilation during exercise than at rest.Support or Funding InformationT.M.S. has been supported by scholarships from FAPESP (2016/01155‐6). The project was funded by FAPESP (2016/01155‐6) and CAPES.