Elevated carotid body tonic activity contributes to ventilatory acclimatization and de-acclimatization to high altitude at rest and during exercise.

Exposure to hypoxia is associated with increased ventilation, which escalates with continued exposure. Carotid chemoreceptors play a critical role in ventilatory acclimatization to prolonged hypoxia in animals. However, the contribution of carotid chemoreceptor tonic activity to ventilatory acclimatization in humans has not been directly demonstrated. We assessed carotid chemoreceptor tonic activity in lowlanders following acclimatization to high altitude and during de-acclimatization. Fourteen healthy participants (7 male, 27 ± 4 years) were assessed at 340 m, following 13 days at high altitude (3800 m), and 3 days post-descent to 1200 m. Carotid chemoreceptor tonic activity was indexed by the two-breath nadir in minute ventilation ( ${\dot{V}}_E$ ) during 1 min of hyperoxia (100% inspired O₂), at rest and during cycling exercise, matched for relative intensity [∼50% maximal oxygen consumption ( ${\dot{V}}_{O_2\max }$ )] and absolute intensity (∼90 W). Resting ${\dot{V}}_E$ increased from sea level (12.9 ± 2.3 l/min) to 3800 m (16.8 ± 3.6 l/min, P < 0.001) and 3-days post-descent (18.2 ± 3.5 l/min, P < 0.001), with no difference between high altitude and post-descent (P = 0.366). The hyperoxic nadir in ventilation was greater than sea level at 3800 m (+153%; P = 0.070, Cohen's d = 1.3) and 3-days post-descent (+74%; P = 0.048), with no significant difference between 3800 m and post-descent (P = 0.326). During 50% ${\dot{V}}_{O_2\max }$ exercise, the hyperoxic ventilation nadir was also greater than sea level at 3800 m (+225%; P = 0.007) and 3 days post-descent (+183%; P = 0.004). The degree of ventilatory acclimatization was associated with the change in the hyperoxic nadir in ventilation (as an index of carotid chemoreceptor tonic activity; r^2 = 0.60, P = 0.014). In conclusion, carotid chemoreceptor tonic activity is elevated and associated with acclimatization to high altitude, and this persists 3 days post-descent. KEY POINTS: Ascent to high altitude is associated with adjustments in ventilation (i.e. ventilatory acclimatization). Heightened carotid chemoreceptor activity plays a critical role in ventilatory acclimatization to prolonged hypoxia in animals; However, there have been no studies in humans directly assessing the contribution of carotid body tonic activity in ventilatory acclimatization during rest and exercise. We aimed to elucidate the changes in carotid chemoreceptor tonic activity in the process of ventilatory acclimatization and de-acclimatization during rest and exercise conditions. Ventilation at rest and during exercise increased at high altitude during acclimatization, and this corresponded with increased inhibition of ventilation with hyperoxia. Increased ventilation persisted at 3 days following descent from high altitude, along with the persistence of elevated carotid body tonic activity. We conclude that elevated carotid body tonic activity plays a major role in ventilatory acclimatization to, and de-acclimatization from, high altitude, and this persists during exercise.