Changes in Heart Rate and Its Regulation by the Autonomic Nervous System Do Not Differ Between Forced and Voluntary Exercise in Mice

Abstract

Most exercise studies in mice have relied on forced training which can introduce psychological stress. Consequently, the utility of mouse models for understanding exercise-mediated effects in humans, particularly autonomic nervous system (ANS) remodeling, have been challenged. We compared the effects of voluntary free-wheel running vs. non-voluntary swimming on heart function in mice with a focus on the regulation of heart rate (HR) by the ANS. Under conditions where the total excess O2 consumption associated with exercise was comparable, the two exercise models led to similar improvements in ventricular function as well as comparable reductions in HR and its control by parasympathetic nervous activity (PNA) and sympathetic nervous activity (SNA), compared to sedentary mice. Both exercise models also increased HR variability (HRV) by similar amounts, independent of HR reductions. In all mice, HRV depended primarily on PNA, with SNA weakly affecting HRV at low frequencies. The differences in both HR and HRV between exercised vs. sedentary mice were eliminated by autonomic blockade, consistent with the similar intrinsic beating rates observed in atria isolated from exercised vs. sedentary mice. In conclusion, both forced and voluntary exercise induce comparable ventricular physiological remodeling as well as HR reductions and HR-independent enhancements of HRV which were both primarily dependent on increased PNA.New and noteworthy–No previous mouse studies have compared the effects of forced and voluntary exercise on the heart function and its modulation by the autonomic nervous system (ANS).–Both voluntary free-wheel running and forced swimming induced similar improvements in ventricular contractile function, reductions in heart rate (HR) and enhancements of HR variability (HRV).–HR regulation in exercised mice was linked to increased parasympathetic nerve activity and reduced sympathetic nerve activity.– HRV was independent of HR and depended primarily on PNA in both exercised and sedentary mice.– Complete cardiac autonomic blockade eliminated differences in both HR and HRV between exercised and sedentary mice.

Adaptation to exercise-induced stress is not dependent on cardiomyocyte α1A-adrenergic receptors

“…Analysis of unblinded data revealed that exercised α 1A -AR knock-down animals had lower heart rates. This was the only parameter of the study that showed an interaction between exercise and genotype, which was not unexpected given that exercise training is known to reduce heart rate [41] and that the SNS and α 1A -ARs have known chronotropic roles [42,43].…”

Effects of enriched environment on micturition activity in freely moving C57BL/6J mice

“…Moreover, Lakin et al reported that heart rate regulation in exercising mice was linked to increased parasympathetic nerve activity and decreased sympathetic nerve activity. 37 Therefore, we speculate that the enhancement of micturition function induced by the EE observed in our study was partly related to the activation of cholinergic nerves due to the activation of parasympathetic nerves. Further studies are necessary to elucidate the relationship between the acetylcholine system and micturition function in mice reared in an EE.…”

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“…Significant elevation in TBARS and CD levels in forced swimming animals may also be due to a result of enhanced catecholamine release from which free radicals may further generate via autooxidation or through metal ion or superoxidecatalyzed oxidation process. Research publications suggest that physical exercise increases catecholamine secretion in the body which releases from sympathetic nerve terminals 43 . Autooxidation of catecholamine to adrenochrome is associated with the formation of superoxide radical and at the same time oxidation of catecholamines which augments the generation of free radical products 44 .…”