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.
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