Comprehensive analysis of voluntary wheel training effects on neural control of the heart rate in rats

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Abstract

Aerobic physical training is used to prevent and correct many cardiovascular disorders. To study the effects of such physical exercise, various methods of training are used in rodents, among which voluntary wheel running is of particular interest, because it is close to the natural rat locomotion in terms of the pattern of motor activity and is devoid of stressful influence. The aim of this work was a comprehensive study of the effects of wheel running on the nervous control of heart rate (HR) in rats. At the age of 6 weeks, the animals were divided into two groups: training (TR, free access to wheels, n = 11) and sedentary control (CON, n = 12). After 6 weeks of training, ECG was recorded in freely moving rats using skin electrodes in baseline, after blockade of cardiac nervous influences and under air-jet stress (4 min). The effects of the autonomic nervous system were analyzed by administering a β1-adrenergic blocker and a peripherally acting M-cholinoceptor blocker, and by analyzing cardiac rhythm variability using spectral and wavelet analyses. TR group showed a decrease in the baseline HR level compared to the CON group. The decrease in HR upon administration of atenolol (2 mg/kg) did not differ between the groups, but methylatropine (1 mg/kg) caused a more significant increase in HR in the TR group than in the CON group. With the combined action of atenolol and methylatropine, HR levels did not differ between the groups. The rats of the TR group showed an increase in the contribution of high-frequency (0.75–3 Hz) oscillations to the total spectrum power of the RR interval. During air-jet stress, TR group showed a more pronounced increase in HR compared to the CON group. In addition, in the TR group, a decrease in the amplitude of HR high-frequency oscillations was observed during stress, while in the CON group, such a decrease was absent. Thus, the voluntary wheel running is accompanied in the rat by an increase in parasympathetic influences on the heart, which is manifested in an increase in respiratory sinus arrhythmia and in an increase in vagal influence on the resting HR level. Moderate bradycardia at rest provides the possibility of a more pronounced increase in HR during emotional stress because of the suppression of parasympathetic cardiac influences.

About the authors

А. А. Borzykh

Institute of Biomedical Problems, Russian Academy of Sciences

Email: ost.msu@gmail.com
Russian Federation, Moscow

Е. К. Selivanova

Lomonosov Moscow State University

Email: ost.msu@gmail.com
Russian Federation, Moscow

А. S. Borovik

Institute of Biomedical Problems, Russian Academy of Sciences

Email: ost.msu@gmail.com
Russian Federation, Moscow

I. V. Kuzmin

Lomonosov Moscow State University

Email: ost.msu@gmail.com
Russian Federation, Moscow

О. L. Vinogradova

Institute of Biomedical Problems, Russian Academy of Sciences

Email: ost.msu@gmail.com
Russian Federation, Moscow

О. S. Tarasova

Institute of Biomedical Problems, Russian Academy of Sciences; Lomonosov Moscow State University

Author for correspondence.
Email: ost.msu@gmail.com
Russian Federation, Moscow; Moscow

References

  1. Li G, Li J, Gao F (2020) Exercise and Cardiovascular Protection. Adv Exp Med Biol 1228: 205–216. https://doi.org/10.1007/978-981-15-1792-1_14
  2. Ruegsegger GN, Booth FW (2018) Health Benefits of Exercise. Cold Spring Harb Perspect Med 8. https://doi.org/10.1101/CSHPERSPECT.A029694
  3. Poole D, Copp S, Colburn T, Craig J, Allen D, Sturek D, O’Leary D, Zucker I, Musch T (2020) Guidelines for animal exercise and training protocols for cardiovascular studies. Am J Physiol Heart Circ Physiol 318: H1100–H1138. https://doi.org/10.1152/AJPHEART.00697.2019
  4. Borzykh AA, Kuzmin IV, Nesterenko AM, Selivanova EK, Martyanov AA, Nikolaev GM, Mamonov PA, Sharova AP, Tarasova OS (2017) Dynamics of rats’ voluntary run characteristics following 8 weeks of training. Aviakosmich Ekol Med 51: 66–73. https://doi.org/10.21687/0233-528X-2017-51-3-66-73
  5. Borzykh AA, Gaynullina DK, Shvetsova AA, Kiryukhina OO, Kuzmin IV, Selivanova EK, Nesterenko AM, Vinogradova OL, Tarasova OS (2022) Voluntary wheel exercise training affects locomotor muscle, but not the diaphragm in the rat. Front Physiol 13: 1003073. https://doi.org/10.3389/fphys.2022.1003073
  6. Sato C, Tanji K, Shimoyama S, Chiba M, Mikami M, Koeda S, Sumigawa K, Akahira K, Yamada J (2020) Effects of voluntary and forced exercises on motor function recovery in intracerebral hemorrhage rats. Neuroreport 31: 189–196. https://doi.org/10.1097/WNR.0000000000001396
  7. Ke Z, Yip SP, Li L, Zheng X-X, Tong K-Y (2011) The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PLoS One 6: e16643. https://doi.org/10.1371/journal.pone.0016643
  8. Pósa A, Szabó R, Kupai K, Baráth Z, Szalai Z, Csonka A, Veszelka M, Gyöngyösi M, Radák Z, Ménesi R, Pávó I, Berkó AM, Varga C (2015) Cardioprotective effects of voluntary exercise in a rat model: role of matrix metalloproteinase-2. Oxid Med Cell Longev 2015: 876805. https://doi.org/10.1155/2015/876805
  9. Beig MI, Callister R, Saint DA, Bondarenko E, Walker FR, Day TA, Nalivaiko E (2011) Voluntary exercise does not affect stress-induced tachycardia, but improves resistance to cardiac arrhythmias in rats. Clin Exp Pharmacol Physiol 38: 19–26. https://doi.org/10.1111/j.1440-1681.2010.05456.x
  10. Gaynullina DK, Borzykh AA, Sofronova SI, Selivanova EK, Shvetsova AA, Martyanov AA, Kuzmin IV, Tarasova OS (2018) Voluntary exercise training restores anticontractile effect of NO in coronary arteries of adult rats with antenatal/early postnatal hypothyroidism. Nitric Oxide 74: 10–18. https://doi.org/10.1016/j.niox.2018.01.001
  11. Gourine AV, Ackland GL (2019) Cardiac vagus and exercise. Physiology 34: 71–80. https://doi.org/10.1152/physiol.00041.2018
  12. Carnevali L, Sgoifo A (2014) Vagal modulation of resting heart rate in rats: the role of stress, psychosocial factors, and physical exercise. Front Physiol 5: 118. https://doi.org/10.3389/fphys.2014.00118
  13. Korsak A, Kellett DO, Aziz Q, Anderson C, D’Souza A, Tinker A, Ackland GL, Gourine AV (2023) Immediate and sustained increases in the activity of vagal preganglionic neurons during exercise and after exercise training. Cardiovasc Res 119: 2329–2341. https://doi.org/10.1093/cvr/cvad115
  14. Coote JH (2010) Recovery of heart rate following intense dynamic exercise. Exp Physiol 95: 431–440. https://doi.org/10.1113/expphysiol.2009.047548
  15. Coote JH, White MJ (2015) CrossTalk proposal: Bradycardia in the trained athlete is attributable to high vagal tone. J Physiol 593: 1745–1747. https://doi.org/10.1113/jphysiol.2014.284364
  16. Neto OB, de Sordi CC, da Mota GR, Marocolo M, Chriguer RS, da Silva VJD (2017) Exercise training improves hypertension-induced autonomic dysfunction without influencing properties of peripheral cardiac vagus nerve. Auton Neurosci Basic Clin 208: 66–72. https://doi.org/10.1016/j.autneu.2017.09.012
  17. Tezini GCSV, Dias DPM, Souza HCD (2013) Aerobic physical training has little effect on cardiovascular autonomic control in aging rats subjected to early menopause. Exp Gerontol 48: 147–153. https://doi.org/10.1016/j.exger.2012.11.009
  18. Mizuno M, Kawada T, Kamiya A, Miyamoto T, Shimizu S, Shishido T, Smith SA, Sugimachi M (2011) Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats. Am J Physiol Regul Integr Comp Physiol 300: 969–977. https://doi.org/10.1152/ajpregu.00768.2010
  19. Medeiros A, Oliveira EM, Gianolla R, Casarini DE, Negrão CE, Brum PC (2004) Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats. Brazil J Med Biol Res 37: 1909–1917. https://doi.org/10.1590/S0100-879X2004001200018
  20. Hsu YC, Tsai SF, Yu L, Chuang JI, Wu F Sen, Jen CJ, Kuo YM (2016) Long-term moderate exercise accelerates the recovery of stress-evoked cardiovascular responses. Stress 19: 125–132. https://doi.org/10.3109/10253890.2015.1108305
  21. Vinogradova OL, Borovik AS, Zhedyaev RYu, Tarasova OS (2024) Respiratory sinus arrhythmia: physiological mechanisms and relationship with systemic blood pressure fluctuations. Human Physiology 50: 276–284. https://doi.org/10.1134/S0362119724700749
  22. D’Souza A, Bucchi A, Johnsen AB, Logantha SJRJ, Monfredi O, Yanni J, Prehar S, Hart G, Cartwright E, Wisloff U, Dobryznski H, Difrancesco D, Morris GM, Boyett MR (2014) Exercise training reduces resting heart rate via downregulation of the funny channel HCN4. Nat Commun 5:3775. https://doi.org/10.1038/ncomms4775
  23. D’Souza A, Sharma S, Boyett MR (2015) CrossTalk opposing view: Bradycardia in the trained athlete is attributable to a downregulation of a pacemaker channel in the sinus node. J Physiol 593: 1749–1751. https://doi.org/10.1113/jphysiol.2014.284356
  24. Negrao CE, Moreira ED, Santos MCLM, Farah VMA, Krieger EM (1992) Vagal function impairment after exercise training. J Appl Physiol 72: 1749–1753. https://doi.org/10.1152/jappl.1992.72.5.1749
  25. Lakin R, Guzman C, Izaddoustdar F, Polidovitch N, Goodman JM, Backx PH (2018) Changes in Heart Rate and Its Regulation by the Autonomic Nervous System Do Not Differ Between Forced and Voluntary Exercise in Mice. Front Physiol 9: 841. https://doi.org/10.3389/fphys.2018.00841
  26. Andreev-Andrievskiy AA, Popova AS, Borovik AS, Dolgov ON, Tsvirkun DV, Custaud M, Vinogradova OL (2014) Stress-associated cardiovascular reaction masks heart rate dependence on physical load in mice. Physiol Behav 132: 1–9. https://doi.org/10.1016/j.physbeh.2014.03.033
  27. Тарасова ОС, Борзых АА, Кузьмин ИВ, Боровик АС, Лукошкова ЕВ, Шарова АП, Виноградова ОЛ, Григорьев АИ (2012) Динамика изменения частоты сердечных сокращений у крыс при ступенчатом изменении скорости бега по беговой дорожке. Рос физиол журн им ИМ Сеченова 98: 1372–1379. [Tarasova OS, Borzykh AA, Kuz’min IV, Borovik AS, Lukoshkova EV, Sharova AP, Vinogradova OL, Grigor’ev AI (2012) Dynamics of heart rate changes in rats following stepwise change of treadmill running speed. Russ J Physiol 98: 1372–1379. (In Russ)]. https://pubmed.ncbi.nlm.nih.gov/23431767
  28. Zhang ZQ, Julien C, Barrès C (1996) Baroreceptor modulation of regional haemodynamic responses to acute stress in rat. J Auton Nerv Syst 60: 23–30. https://doi.org/10.1016/0165-1838(96)00023-9
  29. Witter A, Slangen JL, Terpstra GK (1973) Distribution of 3H-methylatropine in rat brain. Neuropharmacology 12: 835–841. https://doi.org/10.1016/0028-3908(73)90036-1
  30. Brezenoff H, Xiao Y-F, Vargas H (1988) A comparison of the central and peripheral antimuscarinic effects of atropine and methylatropine injected systemically and into the cerebral ventricles. Life Sci 42: 905–911. https://doi.org/10.1016/0024-3205(88)90389-x
  31. Cerutti C, Barres C, Paultre C (1994) Baroreflex modulation of blood pressure and heart rate variabilities in rats: assessment by spectral analysis. Am J Physiol Circ Physiol 266: H1993–H2000. https://doi.org/10.1152/ajpheart.1994.266.5.H1993
  32. Stauss HM (2007) Identification of blood pressure control mechanisms by power spectral analysis. Clin Exp Pharmacol Physiol 34: 362–368. https://doi.org/10.1111/j.1440-1681.2007.04588.x
  33. Sacha J (2014) Interaction between heart rate and heart rate variability. Ann Noninvasiv Electrocardiol 19: 207–216. https://doi.org/10.1111/anec.12148
  34. Negulyaev VO, Tarasova OS, Tarasova NV, Lukoshkova EV, Vinogradova OL, Borovik AS (2019) Phase synchronization of baroreflex oscillations of blood pressure and pulse interval in rats: the effects of cardiac autonomic blockade and gradual blood loss. Physiol Meas 40: 054003. https://doi.org/10.1088/1361-6579/ab10d6
  35. Cohen AH, Gans C (1975) Muscle activity in rat locomotion: movement analysis and electromyography of the flexors and extensors of the elbow. J Morphol 146: 177–196. https://doi.org/10.1002/jmor.1051460202
  36. Srere PA (1969) Citrate Synthase. In: Methods in Enzymology. Acad Press. New York. 3–11.
  37. Faul F, Erdfelder E, Lang AG, Buchner A (2007) G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39: 175–191. https://doi.org/10.3758/BF03193146
  38. Kumae T (2012) Assessment of training effects on autonomic modulation of the cardiovascular system in mature rats using power spectral analysis of heart rate variability. Environ Health Prev Med 17: 415–422. https://doi.org/10.1007/s12199-012-0272-z
  39. Schultz RL, Kullman EL, Waters RP, Huang H, Kirwan JP, Gerdes AM, Swallow JG (2013) Metabolic adaptations of skeletal muscle to voluntary wheel running exercise in hypertensive heart failure rats. Physiol Res 62: 361–369. https://doi.org/10.33549/physiolres.932330
  40. Hawley JA, Hargreaves M, Joyner MJ, Zierath JR (2014) Integrative biology of exercise. Cell 159: 738–749. https://doi.org/10.1016/j.cell.2014.10.029
  41. Morimoto K, Tan N, Nishiyasu T, Sone R, Murakami N (2000) Spontaneous wheel running attenuates cardiovascular responses to stress in rats. Pflugers Arch 440: 216–222. https://doi.org/10.1007/s004240000265
  42. Stauss HM (2014) Heart rate variability: Just a surrogate for mean heart rate? Hypertension 64: 1184–1186. https://doi.org/10.1161/HYPERTENSIONAHA.114.03949
  43. Monfredi O, Lyashkov AE, Johnsen AB, Inada S, Schneider H, Wang R, Nirmalan M, Wisloff U, Maltsev VA, Lakatta EG, Zhang H, Boyett MR (2014) Biophysical characterization of the underappreciated and important relationship between heart rate variability and heart rate. Hypertension 64: 1334–1343. https://doi.org/10.1161/HYPERTENSIONAHA.114.03782
  44. Obrezchikova MN, Tarasova OS, Borovik AS, Koshelev VB (2000) Adaptation to periodic high-altitude hypoxia inhibits baroreflex vagal bradycardia in rats. Bull Exp Biol Med 129: 327–329. https://doi.org/10.1007/BF02439257
  45. Camm A, Malik M, Bigger J (1996) Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J 17: 354–381. https://pubmed.ncbi.nlm.nih.gov/8598068/
  46. Negrao CE, Moreira ED, Brum PC, Denadai ML, Krieger EM (1992) Vagal and sympathetic control of heart rate during exercise by sedentary and exercise-trained rats. Brazil J Med Biol Res 25: 1045–1052. https://pubmed.ncbi.nlm.nih.gov/1342828
  47. Machhada A, Trapp S, Marina N, Stephens RCM, Whittle J, Lythgoe MF, Kasparov S, Ackland GL, Gourine AV (2017) Vagal determinants of exercise capacity. Nat Commun 2017 81(8): 1–7. https://doi.org/10.1038/ncomms15097
  48. Machhada A, Hosford PS, Dyson A, Ackland GL, Mastitskaya S, Gourine AV (2020) Optogenetic Stimulation of Vagal Efferent Activity Preserves Left Ventricular Function in Experimental Heart Failure. JACC Basic to Transl Sci 5: 799–810. https://doi.org/10.1016/j.jacbts.2020.06.002
  49. Ichige MHA, Santos CR, Jordão CP, Ceroni A, Negrão CE, Michelini LC (2016) Exercise training preserves vagal preganglionic neurones and restores parasympathetic tonus in heart failure. J Physiol 594: 6241–6254. https://doi.org/10.1113/JP272730
  50. Dellacqua LO, Gomes PM, Batista JS, Michelini LC, Antunes VR (2024) Exercise-induced neuroplasticity in autonomic nuclei restores the cardiac vagal tone and baroreflex dysfunction in aged hypertensive rats. J Appl Physiol 136: 189–198. https://doi.org/10.1152/japplphysiol.00433.2023
  51. Meeusen R, Duclos M, Foster C, Fry A, Gleeson M, Nieman D, Raglin J, Rietjens G, Steinacker J, Urhausen A, European College of Sport Science, American College of Sports Medicine (2013) Prevention, diagnosis, and treatment of the overtraining syndrome: joint consensus statement of the European College of Sport Science and the American College of Sports Medicine. Med Sci Sports Exerc 45: 186–205. https://doi.org/10.1249/MSS.0b013e318279a10a

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