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

Voluntary apnea markedly attenuates exercise-induced increases in active muscle blood flow, a response known as 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 O₂ partial pressure, which can induce vasoconstriction in active muscles during exercise, we hypothesized that arterial O₂ 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 that reduced end-tidal O₂ partial pressure to ~20 mmHg (i.e., Hypocapnic hyperventilation). As a control trial, hyperventilation was performed while keeping end-tidal O₂ partial pressure at normocapnic level by O₂ 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 hypocapnic than 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 O₂ partial pressure appears to modulate diving reflex–related active muscle hypoperfusion, as well as bradycardia, pressor response, and cerebral hyperemia in exercising adults.