Cardiac Vagus and Exercise

Abstract

Lower resting heart rate and high autonomic vagal activity are strongly associated with superior exercise capacity, maintenance of which is essential for general well-being and healthy aging. Recent evidence obtained in experimental studies using the latest advances in molecular neuroscience, combined with human exercise physiology, physiological modeling, and genomic data suggest that the strength of cardiac vagal activity causally determines our ability to exercise.

Figures

FIGURE 1.

Exercise capacity is reduced in subjects with cardiac vagal dysfunction A: cardiopulmonary exercise test protocol for measuring the speed of heart rate recovery (HRR) after reaching peak tolerance. B: resting heart rate in subjects (n = 1,293), stratified by heart rate recovery 1 min after cessation of cardiopulmonary exercise testing (HRR1). Numbers of subjects are indicated within bars. Resting heart rate is higher in the participants with reduced HRR. C: in the same subjects, percentage population-predicted peak oxygen consumption decreases with reduced HRR. Data are presented as means ± SE. B and C are adapted from Ref. , with permission from Nature Communications.

FIGURE 2.

Autonomic control of the heart during exercise A: schematic representation of the prevailing concept of parasympathetic and sympathetic control of heart rate during exercise. According to this concept, vagal withdrawal is responsible for heart rate increases up to 100 beats/min, followed by activation of the sympathetic input mediating further heart rate increases above 100 beats/min. B: schematic representation of the parasympathetic and sympathetic contributions to the control of heart rate during exercise proposed by White and Raven (89). According to this model, significant cardiac vagal activity is maintained during exercise. In healthy humans, at ~140 beats/min, sympathetic and parasympathetic influences are estimated to be approximately equal in strength, with sympathetic activity dominating heart rate control at higher exercise intensities. Yet, even at high exercise loads, vagal activity continues to modulate cardiac function along with heightened sympathetic activity. Schematic adapted from Ref. , with permission from the Journal of Physiology.

FIGURE 3.

Schematic illustration of dual innervation and key signaling mechanisms underlying control of cardiac function by the autonomic nervous system Reciprocal inhibition prevents competitive effects taking place within the heart and is responsible for the phenomenon of a so-called “accentuated antagonism,” whereby the effect of increased activity of one branch of the autonomic nervous system is accentuated by cross-inhibition of transmitter release by the other branch (51). Mechanisms underlying modulation of G-protein-coupled receptor kinase 2 (GRK2) and β-arrestin-2 (β-arr) expression by the vagus nerve remain to be determined. Cellular mechanisms downstream of cAMP and cGMP generation are not illustrated. AC, adenylyl cyclase; cAMP, cyclic adenosine monophosphate; M2R, muscarinic acetylcholine receptor M2; sGC, soluble guanylyl cyclase; cGMP, cyclic guanosine monophosphate; β-AR, β-adrenoceptor.

FIGURE 4.

Exercise capacity is determined by the activity of vagal preganglionic neurons that reside in the dorsal vagal motor nucleus of the brain stem A: genetic targeting of the dorsal vagal motor nucleus (DVMN) vagal preganglionic neurons in rats to express an inhibitory Gi-protein-coupled Drosophila allatostatin receptor. Left: Schematic drawings of the rat brain in saggital and coronal projections, illustrating the anatomical location of the DVMN. Right: photomicrograph of a representative coronal section of the rat dorsal brain stem, illustrating the distribution of the DVMN neurons transduced to express the receptor in the caudal region of the nucleus. Arrows point at ventrally projecting axons of the transduced vagal neurons (forming the efferent vagus nerve). XII, hypoglossal motor nucleus (cells are not visible); eGFP, enhanced green fluorescence protein; CC, central canal. Scale bar: 200 µm. B: summary data illustrating the effect of allatostatin receptor ligand (insect peptide allatostatin) administration on exercise capacity in rats transduced to express control transgene (left) or allatostatin receptor (right) by the DVMN neurons. Allatostatin binding to allatostatin receptor results in rapid and reversible silencing of mammalian neurons transduced to express this receptor (49, 61). Data are presented as individual values and means ± SE. Comparisons are made using ANOVA. Figure adapted from Ref. , with permission from Nature Communications.