Effect of controlling CO ₂ on peripheral hypercapnic chemosensitivity at exercise intensities above the respiratory compensation point

A rapid change in arterial CO₂ tension causes changes in ventilation, referred to as peripheral hypercapnic chemosensitivity (PHC). The PHC increases from rest to low-intensity exercise yet is not further augmented at higher exercise intensities, where additional ventilatory stimulants are present. During supra-respiratory compensation point (RCP) exercise, as arterial CO₂ tension falls, so does PHC, which may mask the effect of other ventilatory stimuli. Twenty healthy subjects (<i>n</i> = 10 females) completed a maximal exercise test and on subsequent days (<i>days 2</i> and <i>3</i>) had PHC measured at rest, 40% of maximal work rate (Wmax), and supra-RCP exercise intensities. On one experimental day, participants were kept isocapnic, and on the other, end-tidal carbon dioxide ([Formula: see text]) declined naturally during supra-RCP exercise (poikilocapnia). PHC was measured as the quotient between the change in ventilation and [Formula: see text] after two breaths of hypercapnic (10% CO₂) gas delivered 3-5 times during each condition. There was a significant increase in PHC during supra-RCP intensities with isocapnia, compared with poikilocapnic exercise (+11.2 ± 6%) (<i>P</i> = 0.0015). Yet during the isocapnia day, there was still no significant increase in PHC from 40% intensity to supra-RCP (<i>P</i> = 0.96). A repeated-measures correlation demonstrated a significant relationship between PHC and [Formula: see text] during poikilocapnia (<i>r</i> = 0.49, <i>P</i> < 0.001), with no significant relationship during isocapnia (<i>r</i> = 0.06, <i>P</i> = 0.57). We conclude that the metabolic milieu associated with supra-RCP exercise does not impact PHC and there is a CO₂-dependent relationship in which [Formula: see text] influences PHC independent of the initial exercise sensitization.<b>NEW & NOTEWORTHY</b> Maintaining end-tidal carbon dioxide ([Formula: see text]) at isocapnic levels during supra-respiratory compensation point (RCP) exercise significantly increased the peripheral hypercapnic chemoresponse (PHC) compared with poikilocapnic conditions. However, neither the isocapnic nor poikilocapnic exercise above RCP resulted in a significant increase in PHC compared with lower intensity exercise. Thus, although prestimulus [Formula: see text] impacts the PHC, supra-RCP exercise does not further augment the PHC beyond low intensity exercise.