Arterial CO₂ partial pressure is a key modulator of active muscle hypoperfusion mediated by diving reflex in...

Voluntary apnea markedly attenuates exercise-induced increases in active muscle blood flow, a response known as the diving reflex, which is thought to preserve oxygen within the body. However, the underlying mechanisms of this response remain unknown. Since voluntary apnea elevates arterial CO₂ partial pressure, which can induce vasoconstriction in active muscles during exercise, we hypothesized that arterial CO₂ partial pressure modulates diving reflex-related regulation of active muscle blood flow. Fourteen young adults (1 female) performed maximal-duration breath-holding during a dynamic two-legged knee extension exercise that elicits a heart rate of 100 beats·min^-1. The apnea was preceded by 3-min voluntary hyperventilation, which reduced end-tidal CO₂ partial pressure to ∼20 mmHg (i.e., hypocapnic hyperventilation). As a control trial, hyperventilation was performed while keeping the end-tidal CO₂ partial pressure at normocapnic level by CO₂ inhalation (normocapnic hyperventilation). Hypocapnic hyperventilation increased apnea duration compared with normocapnic hyperventilation (52 ± 16 vs. 31 ± 13 s, P < 0.001). At matched time points between conditions, leg blood flow was higher in the hypocapnic than in the normocapnic hyperventilation condition (2236 ± 583 vs. 1643 ± 576 mL·min^-1, P = 0.002). Hypocapnic hyperventilation also attenuated apnea-induced bradycardia, as well as increases in mean arterial pressure and middle cerebral artery mean blood velocity, compared with normocapnic hyperventilation at the iso-time point (all P < 0.001). We show that, based on end-tidal CO₂ measurements, arterial CO₂ partial pressure appears to modulate diving reflex-related active muscle hypoperfusion, as well as bradycardia, pressor response, and cerebral hyperemia in exercising adults.NEW & NOTEWORTHY We show that arterial CO₂ partial pressure is a major factor that largely influences apnea-induced vasoconstriction in exercising muscles as well as bradycardia, pressor responses, and cerebral hyperemia during exercise. Thus, the diving reflex, which is traditionally regarded as an oxygen-conservation response, may also serve to regulate CO₂ homeostasis.