Cerebral blood flow regulation by the muscle metaboreflex during hypocapnic exercise in healthy humans

Abstract

The cerebral blood flow progressively increases from rest to moderate-intensity exercise. Then, during severe-intensity exercise, CBF decreases toward the baseline, indicating that the effect of mechanisms that decrease CBF prevail over those that increase CBF. However, the interplay between mechanisms mediating these opposing effects remains unclear. For instance, hyperventilation-hypocapnia mediates vasoconstriction, which acts toward decreasing CBF. In contrast, metabolite accumulation within contracting skeletal muscles stimulates metabolically sensitive muscle afferents, resulting in sympathetic-induced cardiac output and systemic arterial pressure increase, which, combined, acts toward increasing CBF. Therefore, we sought to test the hypothesis that muscle metaboreflex activation attenuates hyperventilation-induced hypocapnia CBF decrease. Healthy young participants will undergo voluntary hyperventilation to achieve a 10-mmHg reduction in end-tidal CO2, followed by handgrip exercise at 40% of maximum voluntary contraction until task failure. Next, participants will undergo a post-exercise circulatory occlusion maneuver to isolate the muscle metaboreflex activation, or they will experience a free flow control condition, with the order of conditions randomized. Moreover, a cold pressor test (CPT) will evoke a generalized sympathetic activation to assess whether it mitigates hypocapnia-induced CBF reduction as the muscle metaboreflex probably does. This study can provide critical insights into CBF regulation during high-intensity exercise, elucidating the opposing effects of hypocapnia and muscle metaboreflex activation. The findings could enhance our understanding of CBF regulation during high-intensity exercise and offer insights for optimizing CBF management in athletic and clinical settings.