Muscle metaboreflex and autonomic regulation of heart rate in humans

Key points Heart rate increases during exercise due to withdrawal of cardiac parasympathetic tone and increased cardiac sympathetic nerve activity. We investigated the autonomic mechanisms whereby heart rate is regulated by the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreflex). Heart rate responses elicited by partial flow restriction during leg cycling (enhanced metaboreflex activation) and post‐exercise muscle ischemia following leg cycling and handgrip (isolated metaboreflex activation) were evaluated under control (no drug), β‐adrenergic blockade and parasympathetic blockade conditions. We show that the muscle metaboreflex principally elevates heart rate by increasing cardiac sympathetic activity, and only following dynamic exercise with a large muscle mass (post‐exercise muscle ischemia following leg cycling) does the partial withdrawal of cardiac parasympathetic tone make a contribution to this heart rate response. These findings may have implications for patient populations in which alterations in skeletal muscle afferent sensitivity have been identified. Abstract  We elucidated the autonomic mechanisms whereby heart rate (HR) is regulated by the muscle metaboreflex. Eight male participants (22 ± 3 years) performed three exercise protocols: (1) enhanced metaboreflex activation with partial flow restriction (bi‐lateral thigh cuff inflation) during leg cycling exercise, (2) isolated muscle metaboreflex activation (post‐exercise ischaemia; PEI) following leg cycling exercise, (3) isometric handgrip followed by PEI. Trials were undertaken under control (no drug), β 1 ‐adrenergic blockade (metoprolol) and parasympathetic blockade (glycopyrrolate) conditions. HR increased with partial flow restriction during leg cycling in the control condition (Δ11 ± 2 beats min −1 ; P < 0.05). The magnitude of this increase in HR was similar with parasympathetic blockade (Δ11 ± 2 beats min −1 ), but attenuated with β‐adrenergic blockade (Δ4 ± 1 beats min −1 ; P < 0.05 vs . control and parasympathetic blockade). During PEI following leg cycling exercise, HR remained similarly elevated above rest under all conditions (Δ11 ± 2, Δ13 ± 3 and Δ9 ± 4 beats min −1 , for control, β‐adrenergic and parasympathetic blockade; P > 0.05 between conditions). During PEI following handgrip, HR was similarly elevated from rest under control and parasympathetic blockade (Δ4 ± 1 vs . Δ4 ± 2 beats min −1 ; P > 0.05 between conditions) conditions, but attenuated with β‐adrenergic blockade (Δ0.2 ± 1 beats min −1 ; P > 0.05 vs . rest). Thus muscle metaboreflex activation‐mediated increases in HR are principally attributable to increased cardiac sympathetic activity, and only following exercise with a large muscle mass (PEI following leg cycling) is there a contribution from the partial withdrawal of cardiac parasympathetic tone.