Fisher · The Journal of physiology 2010 · controlled crossover physiological study with pharmacological blockade · n=9

Autonomic control of heart rate by metabolically sensitive skeletal muscle afferents in humans.

Cited 136 times in the scientific literature.

Level 3 - non-randomized controlled study

Controlled physiological crossover study with autonomic pharmacological blockades in healthy humans.

PubMed 20142272 · doi:10.1113/jphysiol.2009.185470 · record verified 2026-08-29

What was done

Nine healthy male participants (mean age 23 ± 5 years) underwent isolated activation of the muscle metaboreflex via post-exercise ischaemia (PEI) following moderate (25% maximum voluntary contraction, PEI-M) and high (40% maximum voluntary contraction, PEI-H) intensity isometric handgrip exercise. Testing was performed across three conditions: control (no drug), parasympathetic blockade (glycopyrrolate), and beta-adrenergic blockade (metoprolol or propranolol), while beat-to-beat heart rate (HR) and arterial blood pressure (BP) were continuously measured.

What was found

During control PEI-M, HR increased slightly above baseline (+3 ± 2 beats min⁻¹); this elevation was abolished with beta-adrenergic blockade (P < 0.05 vs. control) and augmented with parasympathetic blockade (+8 ± 2 beats min⁻¹, P < 0.05 vs. control and beta-adrenergic blockade). During control PEI-H, the HR increase was larger (+9 ± 3 beats min⁻¹, P < 0.05 vs. PEI-M), attenuated with beta-adrenergic blockade (+4 ± 2 beats min⁻¹, P < 0.05 vs. control), but unchanged with parasympathetic blockade (+9 ± 2 beats min⁻¹, P > 0.05 vs. control). Arterial blood pressure increased from rest during PEI-M and rose further during PEI-H (P < 0.05) across all conditions.

Why it matters

This study provides direct human evidence that the muscle metaboreflex engages cardiac sympathetic nerve activity to increase heart rate, but that concurrent parasympathetic reactivation masks this response at lower reflex intensities.

Limits

The sample size was very small (n = 9) and included only young adult males, limiting generalizability to females and clinical populations. Two different beta-blockers were used across subjects (metoprolol or propranolol). Specific numerical blood pressure values are not provided in the abstract.

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