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 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.