Muscle chemoreflexes and exercise in humans

Abstract

This review focuses on the role afferent nerves from the contracting muscles play in linking muscle metabolism to the cardiovascular adjustments during exercise by means of a 'muscle chemoreflex'. In the 1930s Alam and Smirk provided the first clear evidence that human (and animal) skeletal muscles are innervated by chemosensitive afferents that can evoke increases in arterial blood pressure. They proposed that the purpose of the increase in pressure was to improve blood flow to the active muscles. Subsequent studies have identified the slowly conducting group IV afferents as the major class of fibres participating in the sensory arm of this reflex. Most of these fibres travel via the dorsal roots to the ipsilateral spinal cord where they synapse in the substantia gelatinosa and release substance P or other peptide transmitters. The second order (or higher) neurons cross to the contralateral side of the spinal cord and travel rostrally to stimulate brainstem cardiovascular centres and increase arterial pressure. Current evidence favours the concept that substances associated with muscle acidosis provide the stimulus to the afferents. In humans, chemosensitive afferent activation causes a marked increase in vasoconstrictor efferent muscle sympathetic nerve activity. It is unclear if the muscle chemoreflex improves blood flow to 'underperfused' active muscles by augmenting arterial pressure, or if the increase in sympathetic outflow restrains metabolic vasodilatation to regulate arterial blood pressure during activities like running or cycling.