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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.

SUBMITTER: Lakin R

PROVIDER: S-EPMC6055008 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Lakin Robert R Guzman Camilo C Izaddoustdar Farzad F Polidovitch Nazari N Goodman Jack M JM Backx Peter H PH

Frontiers in physiology 20180716

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 O<sub>2</su ...[more]

PMID: 30061838

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Project description:BACKGROUND:The strategy of adaptation of the human body in microgravity is largely associated with the plasticity of cardiovascular system regulatory mechanisms. During long-term space flights the changes in the stroke volume of the heart are observed, the heart rate decreases, the phase structure of cardiac cycle is readjusted The purpose of this work was to clarify urine proteome changes associated with the initial condition of the heart rate autonomic regulation mechanisms in cosmonauts who have participated in long space missions. Urine proteome of each cosmonaut was analyzed before and after space flight, depending on the initial parameters characterizing the regulatory mechanisms of the cardiovascular system. RESULTS:The proteins cadherin-13, mucin-1, alpha-1 of collagen subunit type VI (COL6A1), hemisentin-1, semenogelin-2, SH3 domain-binding protein, transthyretin and serine proteases inhibitors realize a homeostatic role in individuals with different initial type of the cardiovascular system regulation. The role of significantly changed urine proteins in the cardiovascular homeostasis maintenance is associated with complex processes of atherogenesis, neoangiogenesis, activation of calcium channels, changes in cell adhesion and transmembrane properties, changes in extracellular matrix, participation in protection from oxidative stress and leveling the effects of hypoxia. Therefore, the concentrations of these proteins significantly differ between groups with dominant parasympathetic and sympathetic influences. CONCLUSION:The space flight induced urine proteome changes are significantly different in the groups identified by heart rate autonomic regulation peculiarities before space flight. All these proteins regulate the associated biological processes which affect the stiffness of the vascular wall, blood pressure level, the severity of atherosclerotic changes, the rate and degree of age-related involution of elastin and fibulin, age-related increase in collagen stiffness, genetically determined features of elastin fibers. The increased vascular rigidity (including the aorta) and of myocardium may be regarded as a universal response to various extreme factors. Significant differences in the semi-quantitative analysis of signal proteins between groups with different types of autonomic regulation are explained by a common goal: to ensure optimal adaptation regardless of age and of the genetically determined type of responses to the extreme environmental factors effects.

Project description:Physical exercise has been shown to modulate activity within the autonomic nervous system (ANS). Considering physical exercise as a holistic stimulus on the nervous system and specifically the ANS, uni- and multimodal analysis tools were applied to characterize centrally driven interactions and control of ANS functions. Nineteen young and physically active participants performed treadmill tests at individually determined moderate and high intensities. Continuous electrodermal activity (EDA), heart rate (HR), and skin temperature at wrist (Temp) were recorded by wireless multisensor devices (Empatica® E4, Milan, Italy) before and 30 min after exercise. Artifact-free continuous 3 min intervals were analyzed. For unimodal analysis, mean values were calculated, for bimodal and multimodal analysis canonical correlation analysis (CCA) was performed. Unimodal results indicate that physical exercise affects ANS activity. More specifically, Temp increased due to physical activity (moderate intensity: from 34.15°C to 35.34°C and high intensity: from 34.11°C to 35.09°C). HR increased more for the high (from 60.76 bpm to 79.89 bpm) than for the moderate (from 64.81 bpm to 70.83 bpm) intensity. EDA was higher for the high (pre: 8.06 μS and post: 9.37 μS) than for the moderate (pre: 4.31 μS and post: 3.91 μS) intensity. Bimodal analyses revealed high variations in correlations before exercise. The overall correlation coefficient showed varying correlations in pretest measures for all modality pairs (EDA-HR, HR-Temp, Temp-EDA at moderate: 0.831, 0.998, 0.921 and high: 0.706, 0, 0.578). After exercising at moderate intensity coefficients changed little (0.828, 0.744, 0.994), but increased substantially for all modality pairs after exercising at high intensity (0.976, 0.898, 0.926). Multimodal analysis confirmed bimodal results. Exercise-induced changes in ANS activity can be found in multiple ANS modalities as well as in their interactions. Those changes are intensity-specific: with higher intensity the interactions increase. Canonical correlations between different ANS modalities may therefore offer a feasible approach to determine exercise induced modulations of ANS activity.

Project description:Previous treadmill exercise studies showing neuroprotective effects have raised questions as to whether exercise or the stress related to it may be key etiologic factors. In this study, we examined different exercise regimens (forced and voluntary exercise) and compared them with the effect of stress-only on stroke protection. Adult male Sprague-Dawley rats (n = 65) were randomly assigned to treatment groups for 3 weeks. These groups included control, treadmill exercise, voluntary running wheel exercise, restraint, and electric shock. Levels of the stress hormone, corticosterone, were measured in the different groups using ELISA. Animals from each group were then subjected to stroke induced by a 2-h middle cerebral artery (MCA) occlusion followed by 48-h reperfusion. Infarct volume was determined in each group, while changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR between voluntary and treadmill exercise groups. The level of corticosterone was significantly higher in both stress (P < 0.05) and treadmill exercise (P < 0.05) groups, but not in the voluntary exercise group. Infarct volume was significantly reduced (P < 0.01) following stroke in rats exercised on a treadmill. However, the amelioration of damage was not duplicated in voluntary exercise, even though running distance in the voluntary exercise group was significantly (P < 0.01) longer than that of the forced exercise group (4,828 vs. 900 m). Furthermore, rats in the electric shock group displayed a significantly increased (P < 0.01) infarct volume. Expression of both Hsp 27 and Hsp 70 mRNA was significantly increased (P < 0.01) in the treadmill exercise group as compared with that in the voluntary exercise group. These results suggest that exercise with a stressful component, rather than either voluntary exercise or stress alone, is better able to reduce infarct volume. This exercise-induced neuroprotection may be attributable to up-regulation of stress-induced heat shock proteins 27 and 70.

Project description:OBJECTIVES:Glucagon-like peptide-1 (GLP-1) is secreted from enteroendocrine cells and exerts a broad number of metabolic actions through activation of a single GLP-1 receptor (GLP-1R). The cardiovascular actions of GLP-1 have garnered increasing attention as GLP-1R agonists are used to treat human subjects with diabetes and obesity that may be at increased risk for development of heart disease. Here we studied mechanisms linking GLP-1R activation to control of heart rate (HR) in mice. METHODS:The actions of GLP-1R agonists were examined on the control of HR in wild type mice (WT) and in mice with cardiomyocyte-selective disruption of the GLP-1R (Glp1rCM-/-). Complimentary studies examined the effects of GLP-1R agonists in mice co-administered propranolol or atropine. The direct effects of GLP-1R agonism on HR and ventricular developed pressure were examined in isolated perfused mouse hearts ex vivo, and atrial depolarization was quantified in mouse hearts following direct application of liraglutide to perfused atrial preparations ex vivo. RESULTS:Doses of liraglutide and lixisenatide that were equipotent for acute glucose control rapidly increased HR in WT and Glp1rCM-/- mice in vivo. The actions of liraglutide to increase HR were more sustained relative to lixisenatide, and diminished in Glp1rCM-/- mice. The acute chronotropic actions of GLP-1R agonists were attenuated by propranolol but not atropine. Neither native GLP-1 nor lixisenatide increased HR or developed pressure in perfused hearts ex vivo. Moreover, liraglutide had no direct effect on sinoatrial node firing rate in mouse atrial preparations ex vivo. Despite co-localization of HCN4 and GLP-1R in primate hearts, HCN4-directed Cre expression did not attenuate levels of Glp1r mRNA transcripts, but did reduce atrial Gcgr expression in the mouse heart. CONCLUSIONS:GLP-1R agonists increase HR through multiple mechanisms, including regulation of autonomic nervous system function, and activation of the atrial GLP-1R. Surprisingly, the isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.

Project description:IntroductionStress is a major health issue in adolescents owing to the important transitions experienced during this period. Aromatherapy is an effective method for the reduction of stress in adolescents.PurposeThe aims of this study were to examine the effect of aromatherapy on the regulation of the autonomic nervous system (ANS) along with stress relief and to explore the effect of aromatherapy on adolescents with different levels of stress.MethodsThis quasi-experimental study comprised three types of treatments: control (no essential oil), pure essential oil therapy (sandalwood), and blended essential oil therapy (sandalwood-lavender). The heart rate variability (HRV) was calculated to evaluate the post-exercise recovery of the ANS to the baseline level in the recruited adolescents. To examine the efficiency of aromatherapy, Friedman test was used to assess the significance of difference in all parameters (i.e., mean heart rate, SDNN, normalized LF, normalized HF, and LF/HF) between baseline and after exercise among the three treatment conditions.ResultsThe participants comprised 43 junior college students (8 males and 35 females) with a mean age of 18.21 ± 0.99. Significant differences in changes of two HRV parameters (normalized LF and LF/HF) were associated with both essential oil therapies compared to those in the control group (p<0.05), and one more HRV parameter (normalized HF) exhibited significant difference related to blended essential oil therapy compared to that of the control group. Besides, changes in two HRV parameters (mean heart rate and normalized HF) of both essential oil therapies in the low level stress subgroup showed significant differences compared to those of the control group (p<0.05).ConclusionsThis study demonstrated that aromatherapy could be used for ANS regulation with stress-relieving effects in adolescents. The participants with a low stress level appeared to respond better to the blended essential oil therapy, whereas those with medium to high levels of stress appeared to respond poorly to aromatherapy compared to the control.

Dataset Information

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

Publications

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

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