Hypercapnic ventilatory chemoreflex sensitivity increases with exercise intensities up to the respiratory compensation point

The hypercapnic ventilatory chemoreflex response (HCVR), a mechanism for maintaining arterial blood gas homeostasis during exercise, is known to increase from rest to exercise; however, it remains unclear whether this response becomes further sensitized with increasing intensities below the respiratory compensation point (RCP), a critical threshold in exercise physiology that delineates shifts in ventilatory control. Twenty-three healthy young participants (mean±SD: age=23±4 years, V˙O 2max =42.0±8.2 mL·kg -1 ·min -1 , 12 females) completed a maximal cycling exercise protocol (Visit 1) and three, repeated step-incremental protocols (Visits 2-4) over three days. The step-incremental protocol involved two, 8-min stages in the lower and upper regions of the moderate-intensity domain (MOD 1 and MOD 2 , i.e., below lactate threshold, LT) and two, 12-min stages within the heavy-intensity domain (HVY 1 and HVY 2 , i.e., between LT and RCP). Arterialized-venous blood samples were obtained from a dorsal hand vein catheter, with the hand warmed to ensure arterialization (Visit 2). At three time points during steady-state exercise at each intensity (Visits 3 and 4), hypercapnia was administered for ~20 s (6-8 breaths) by rebreathing from a bag containing 22% O 2 , 4% CO 2 and balanced N 2 . Throughout exercise, gas exchange and ventilatory variables were measured breath-by-breath by metabolic cart and pneumotach. At each intensity, HCVR was determined as the slope of the ventilation (V· E ) vs. end-tidal CO 2 pressure (P ET CO 2 ) relationship (V· E S, L·min -1 ·mmHg -1 ) from the average of the six repeated trials. One-way repeated measures analysis of variance investigated between-intensity differences in arterialized blood gas measures and HCVR. The average arterial [H + ] at MOD 1 was 39.5±1.5 nM and rose significantly (p<0.001) to 40.5±1.9, 41.5±2.4, and 42.7±3.1 nM at MOD 2 , HVY 1 , and HVY 2 , respectively whereas mean PaCO 2 decreased from 40.8±2.4 mmHg in MOD 1 to 40.6±2.7, 39.4±2.7, and 37.3±2.7 mmHg. At MOD 1 , the average V· E S was 2.4±0.9 L·min -1 ·mmHg -1 and increased with intensity (p<0.001) to 2.8±0.8, 3.3±0.9, and 3.8±1.7 L·min -1 ·mmHg -1 at MOD 2 , HVY 1 , and HVY 2 , respectively. The P ET O 2 was normoxic and did not change (p=0.200) with intensity (MOD 1 : P ET O 2 = 106±8 mmHg; MOD 2 : P ET O 2 = 104±7; HVY 1 : P ET O 2 = 103±8; HVY 2 : P ET O 2 = 105±8). HCVR progressively increased with higher steady-state exercise intensities suggesting that the peripheral chemoreflex is increasingly sensitized. Whether such sensitization is necessary to maintain arterial blood gas homeostasis during exercise up to RCP warrants further investigation. DAK: NSERC Discovery Grant (RGPIN-2021-03980) and by the Canadian Foundation for Innovation John Evans Leadership Fund (Project: 42544). NAG: OGS and NSERC CGS-D Award. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.