Welcome the carotid chemoreflex to the ‘neural control of the circulation during exercise’ club

Abstract

Chemoreceptors in the brain (central chemoreceptors) and in the carotid sinus (peripheral chemoreceptors) are known to exert powerful influence over autonomic control during exposure to hypercapnia and hypoxia, respectively. However, the contributionofchemoreceptorstotheautonomic response to exercise, and thus its influence on the cardiovascular response to exercise, has not received much attention. Stickland et al. (2007) showed for the first time that the inhibition of carotid chemoreceptors by closed-carotid infusion of dopamine or hyperoxic Ringer solution at rest did not change blood flow and conductance in the hindlimb of healthy dogs, but caused an immediate vasodilatory response in the hindlimb of dogs with heart failure. During mild exercise, inhibitionofcarotidchemoreceptorscaused vasodilatation in the hindlimb of both healthy dogs and dogs with heart failure. In addition, it was shown that this response was entirely attributed to a decrease in the sympathetic restraint of skeletal muscle blood flow during exercise, since the vasodilatory response was abolished after infusion of an alpha adrenergic blocker (phentolamine) both in healthy dogs and in dogs with heart failure. Thereafter,Sticklandetal.(2008)elegantly translated these findings to exercising healthy humans. They showed that the transient inhibition of the carotid chemoreceptors by inhalation of hyperoxic gas during dynamic handgrip exercise reduced muscle sympathetic nerve activity (MSNA) by approximately 35%, while the transient stimulation of the carotid chemoreceptors by inhalation of hypoxic gas increased MSNA with a similar time delay to that obtained with carotid chemoreceptors inhibition via hyperoxia. Hence, these results highlighted the important role of the carotid chemoreflex in regulating the sympathoexcitation during exercise in healthy humans. Nonetheless, at this point, it was not known if the carotid chemoreceptors indeed influence skeletal muscle bloodflowandvascularconductanceduring exercise in humans.