Skip to main content
SpringerLink
Log in

One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats

  • Original Article
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Aerobic exercise training induces a unique cardioprotective phenotype, but it is becoming clear that it does not promote the same structural, functional, and molecular adaptations in both ventricles. In the present study, we aimed to better characterize and compare the molecular pathways involved in the exercise-induced remodeling of both ventricles. Female Sprague-Dawley rats were randomly assigned to control and exercise groups. Animals in the exercise group were submitted to low-intensity treadmill exercise for 54 weeks. After the experimental period, biventricular hemodynamic analysis was performed and right and left ventricles were harvested for morphological and biochemical analyses. Data showed that long-term low-intensity exercise training improves cardiac function, especially left ventricular diastolic function; however, the expression of connexin-43, CCAAT-enhancer binding protein β, and c-kit did not change in none of the ventricles. In the right ventricle, long-term exercise training induced an increase of manganese superoxide dismutase and sirtuin 3 protein expression, suggestive of improved antioxidant capacity. Our results also support that long-term aerobic exercise training imposes greater metabolic remodeling to the right ventricle, mainly by increasing mitochondrial ability to produce ATP, with no association to estrogen-related receptor α regulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Aaron CP, Tandri H, Barr RG, Johnson WC, Bagiella E, Chahal H, Jain A, Kizer JR, Bertoni AG, Lima JAC, Bluemke DA, Kawut SM (2011) Physical activity and right ventricular structure and function: the MESA-Right Ventricle Study. Am J Respir Crit Care Med 183:396–404. https://doi.org/10.1164/rccm.201003-0469OC

    Article  PubMed  Google Scholar 

  2. Amado FM, Barros A, Azevedo AL, Vitorino R, Ferreira R (2014) An integrated perspective and functional impact of the mitochondrial acetylome. Expert Rev Proteomics 11:383–394. https://doi.org/10.1586/14789450.2014.899470

    Article  CAS  PubMed  Google Scholar 

  3. Antunes D, Padrao AI, Maciel E, Santinha D, Oliveira P, Vitorino R, Moreira-Goncalves D, Colaco B, Pires MJ, Nunes C, Santos LL, Amado F, Duarte JA, Domingues MR, Ferreira R (2014) Molecular insights into mitochondrial dysfunction in cancer-related muscle wasting. Biochim Biophys Acta 1841:896–905. https://doi.org/10.1016/j.bbalip.2014.03.004

    Article  CAS  PubMed  Google Scholar 

  4. Arbab-Zadeh A, Perhonen M, Howden E, Peshock RM, Zhang R, Adams-Huet B, Haykowsky MJ, Levine BD (2014) Cardiac remodeling in response to 1 year of intensive endurance training. Circulation 130:2152–2161. https://doi.org/10.1161/CIRCULATIONAHA.114.010775

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bal MP, de Vries WB, van der Leij FR, van Oosterhout MF, Baan J, van der Wall EE, van Bel F, Steendijk P (2005) Left ventricular pressure-volume relationships during normal growth and development in the adult rat-studies in 8- and 50-week-old male Wistar rats. Acta Physiol Scand 185:181–191. https://doi.org/10.1111/j.1365-201X.2005.01484.x

    Article  CAS  PubMed  Google Scholar 

  6. Beery AK, Zucker I (2011) Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev 35:565–572. https://doi.org/10.1016/j.neubiorev.2010.07.002

    Article  Google Scholar 

  7. Benito B, Gay-Jordi G, Serrano-Mollar A, Guasch E, Shi Y, Tardif JC, Brugada J, Nattel S, Mont L (2011) Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training. Circulation 123:13–22. https://doi.org/10.1161/CIRCULATIONAHA.110.938282

    Article  PubMed  Google Scholar 

  8. Bishop DJ, Granata C, Eynon N (2014) Can we optimise the exercise training prescription to maximise improvements in mitochondria function and content? Biochim Biophys Acta 1840:1266–1275. https://doi.org/10.1016/j.bbagen.2013.10.012

    Article  CAS  PubMed  Google Scholar 

  9. Boström P, Mann N, Wu J, Quintero PA, Plovie ER, Panáková D, Gupta RK, Xiao C, MacRae CA, Rosenzweig A, Spiegelman BM (2010) C/EBPβ controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell 143:1072–1083. https://doi.org/10.1016/j.cell.2010.11.036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chang Y, Yu T, Yang H, Peng Z (2015) Exhaustive exercise-induced cardiac conduction system injury and changes of cTnT and Cx43. Int J Sports Med 36:1–8. https://doi.org/10.1055/s-0034-1384545

    Article  CAS  PubMed  Google Scholar 

  11. Clayton JA, Collins FS (2014) NIH to balance sex in cell and animal studies. Nature 509:282–283

    Article  Google Scholar 

  12. Coore HG, Denton RM, Martin BR, Randle PJ (1971) Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. Biochem J 125:115–127. https://doi.org/10.1042/bj1250115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ferreira R, Vitorino R, Padrao AI, Espadas G, Mancuso FM, Moreira-Goncalves D, Castro-Sousa G, Henriques-Coelho T, Oliveira PA, Barros AS, Duarte JA, Sabido E, Amado F (2014) Lifelong exercise training modulates cardiac mitochondrial phosphoproteome in rats. J Proteome Res 13:2045–2055. https://doi.org/10.1021/pr4011926

    Article  CAS  PubMed  Google Scholar 

  14. Ferreira R, Moreira-Goncalves D, Azevedo AL, Duarte JA, Amado F, Vitorino R (2015) Unraveling the exercise-related proteome signature in heart. Basic Res Cardiol 110:454. https://doi.org/10.1007/s00395-014-0454-5

    Article  CAS  PubMed  Google Scholar 

  15. Ferreira R, Nogueira-Ferreira R, Trindade F, Vitorino R, Powers SK, Moreira-Gonçalves D (2018) Sugar or fat: the metabolic choice of the trained heart. Metabol Clin Exp 87:98–104. https://doi.org/10.1016/j.metabol.2018.07.004

    Article  CAS  Google Scholar 

  16. Finocchiaro G, Dhutia H, D’Silva A, Malhotra A, Steriotis A, Millar L, Prakash K, Narain R, Papadakis M, Sharma R, Sharma S (2017) Effect of sex and sporting discipline on LV adaptation to exercise. JACC Cardiovasc Imaging 10:965–972. https://doi.org/10.1016/j.jcmg.2016.08.011

    Article  PubMed  Google Scholar 

  17. Foryst-Ludwig A, Kreissl MC, Sprang C, Thalke B, Böhm C, Benz V, Gürgen D, Dragun D, Schubert C, Mai K, Stawowy P, Spranger J, Regitz-Zagrosek V, Unger T, Kintscher U (2011) Sex differences in physiological cardiac hypertrophy are associated with exercise-mediated changes in energy substrate availability. Am J Physiol Heart Circ Physiol 301:H115–H122. https://doi.org/10.1152/ajpheart.01222.2010

    Article  CAS  PubMed  Google Scholar 

  18. Heidbuchel H, Hoogsteen J, Fagard R, Vanhees L, Ector H, Willems R, Van Lierde J (2003) High prevalence of right ventricular involvement in endurance athletes with ventricular arrhythmias. Role of an electrophysiologic study in risk stratification. Eur Heart J 24:1473–1480. https://doi.org/10.1016/S0195-668X(03)00282-3

    Article  PubMed  Google Scholar 

  19. Heiskanen MA, Leskinen T, Heinonen IHA, Löyttyniemi E, Eskelinen J-J, Virtanen K, Hannukainen JC, Kalliokoski KK (2016) Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men. Am J Physiol Heart Circ Physiol 311:H667–H675. https://doi.org/10.1152/ajpheart.00399.2016

    Article  PubMed  Google Scholar 

  20. Jones SA (2006) Ageing to arrhythmias: conundrums of connections in the ageing heart. J Pharm Pharmacol 58:1571–1576. https://doi.org/10.1211/jpp.58.12.0002

    Article  CAS  PubMed  Google Scholar 

  21. Kararigas G, Leber J, Schubert C, Fliegner D, Mahmoodzadeh S, Regitz-Zagrosek V, Dworatzek E, Kusch A, Dragun D, Westphal C, Moulin M, Ventura-Clapier R, Gustafsson J-A, Davidson MM (2014) Sex differences in exercise-induced physiological myocardial hypertrophy are modulated by oestrogen receptor beta. Cardiovasc Res 102:418–428. https://doi.org/10.1093/cvr/cvu065

    Article  CAS  PubMed  Google Scholar 

  22. La Gerche A, Burns AT, Mooney DJ, Inder WJ, Taylor AJ, Bogaert J, Macisaac AI, Heidbuchel H, Prior DL (2012) Exercise-induced right ventricular dysfunction and structural remodelling in endurance athletes. Eur Heart J 33:998–1006. https://doi.org/10.1093/eurheartj/ehr397

    Article  CAS  PubMed  Google Scholar 

  23. La Gerche A, Roberts T, Claessen G (2014) The response of the pulmonary circulation and right ventricle to exercise: exercise-induced right ventricular dysfunction and structural remodeling in endurance athletes (2013 Grover Conference series). Pulm Circ 4:407–416. https://doi.org/10.1086/677355

    Article  PubMed  PubMed Central  Google Scholar 

  24. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685. https://doi.org/10.1038/227680a0

    Article  CAS  Google Scholar 

  25. Lam CS, Borlaug BA, Kane GC, Enders FT, Rodeheffer RJ, Redfield MM (2009) Age-associated increases in pulmonary artery systolic pressure in the general population. Circulation 119:2663–2670. https://doi.org/10.1161/CIRCULATIONAHA.108.838698

    Article  PubMed  PubMed Central  Google Scholar 

  26. Lawler JM, Powers SK, Hammeren J, Martin AD (1993) Oxygen cost of treadmill running in 24-month-old Fischer-344 rats. Med Sci Sports Exerc 25:1259–1264. https://doi.org/10.1249/00005768-199311000-00009

    Article  CAS  PubMed  Google Scholar 

  27. Lerchenmuller C, Rosenzweig A (2014) Mechanisms of exercise-induced cardiac growth. Drug Discov Today 19:1003–1009. https://doi.org/10.1016/j.drudis.2014.03.010

    Article  CAS  PubMed  Google Scholar 

  28. Li L, Muhlfeld C, Niemann B, Pan R, Li R, Hilfiker-Kleiner D, Chen Y, Rohrbach S (2011) Mitochondrial biogenesis and PGC-1alpha deacetylation by chronic treadmill exercise: differential response in cardiac and skeletal muscle. Basic Res Cardiol 106:1221–1234. https://doi.org/10.1007/s00395-011-0213-9

    Article  CAS  PubMed  Google Scholar 

  29. Loffredo FS, Nikolova AP, Pancoast JR, Lee RT (2014) Heart failure with preserved ejection fraction: molecular pathways of the aging myocardium. Circ Res 115:97–107. https://doi.org/10.1161/CIRCRESAHA.115.302929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mann N, Rosenzweig A (2012) Can exercise teach us how to treat heart disease? Circulation 126:2625–2635. https://doi.org/10.1161/CIRCULATIONAHA.111.060376

    Article  PubMed  PubMed Central  Google Scholar 

  31. Moreira-Goncalves D, Henriques-Coelho T, Fonseca H, Ferreira RM, Amado F, Leite-Moreira A, Duarte JA (2011) Moderate exercise training provides left ventricular tolerance to acute pressure overload. Am J Physiol Heart Circ Physiol 300:H1044–H1052. https://doi.org/10.1152/ajpheart.01008.2010

    Article  CAS  PubMed  Google Scholar 

  32. Moreira-Goncalves D, Henriques-Coelho T, Fonseca H, Ferreira R, Padrao AI, Santa C, Vieira S, Silva AF, Amado F, Leite-Moreira A, Duarte JA (2015) Intermittent cardiac overload results in adaptive hypertrophy and provides protection against left ventricular acute pressure overload insult. J Physiol 593:3885–3897. https://doi.org/10.1113/JP270685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Moreira-Goncalves D, Ferreira R, Fonseca H, Padrao AI, Moreno N, Silva AF, Vasques-Novoa F, Goncalves N, Vieira S, Santos M, Amado F, Duarte JA, Leite-Moreira AF, Henriques-Coelho T (2015) Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension. Basic Res Cardiol 110:57. https://doi.org/10.1007/s00395-015-0514-5

    Article  CAS  PubMed  Google Scholar 

  34. Murphy E (2011) Estrogen signaling and cardiovascular disease. Circ Res 109:687–696. https://doi.org/10.1161/circresaha.110.236687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Naderi N, Hemmatinafar M, Gaeini AA, Bahramian A, Ghardashi-Afousi A, Kordi MR, Darbandi-Azar A, Karimzade F, Mohebbi H, Barati M (2019) High-intensity interval training increase GATA4, CITED4 and c-kit and decreases C/EBPβ in rats after myocardial infarction. Life Sci 221:319–326. https://doi.org/10.1016/j.lfs.2019.02.045

    Article  CAS  PubMed  Google Scholar 

  36. Nogueira-Ferreira R, Moreira-Goncalves D, Silva AF, Duarte JA, Leite-Moreira A, Ferreira R, Henriques-Coelho T (2016) Exercise preconditioning prevents MCT-induced right ventricle remodeling through the regulation of TNF superfamily cytokines. Int J Cardiol 203:858–866. https://doi.org/10.1016/j.ijcard.2015.11.066

    Article  PubMed  Google Scholar 

  37. Ozturk N, Olgar Y, Er H, Kucuk M, Ozdemir S (2017) Swimming exercise reverses aging-related contractile abnormalities of female heart by improving structural alterations. Cardiol J 24:85–93. https://doi.org/10.5603/CJ.a2016.0069

    Article  PubMed  Google Scholar 

  38. Padrão AI, Ferreira RMP, Vitorino R, Alves RMP, Neuparth MJ, Duarte JA, Amado F (2011) OXPHOS susceptibility to oxidative modifications: the role of heart mitochondrial subcellular location. Biochim Biophys Acta 1807:1106–1113. https://doi.org/10.1016/j.bbabio.2011.04.002

    Article  CAS  PubMed  Google Scholar 

  39. Powers SK, Smuder AJ, Kavazis AN, Quindry JC (2014) Mechanisms of exercise-induced cardioprotection. Physiology (Bethesda) 29:27–38. https://doi.org/10.1152/physiol.00030.2013

    Article  CAS  Google Scholar 

  40. Sanz-de la Garza M, Rubies C, Batlle M, Bijnens BH, Mont L, Sitges M, Guasch E (2017) Severity of structural and functional right ventricular remodeling depends on training load in an experimental model of endurance exercise. Am J Physiol Heart Circ Physiol 313:H459–H468. https://doi.org/10.1152/ajpheart.00763.2016

    Article  PubMed  Google Scholar 

  41. Scharhag J, Schneider G, Urhausen A, Rochette V, Kramann B, Kindermann W (2002) Athlete’s heart: right and left ventricular mass and function in male endurance athletes and untrained individuals determined by magnetic resonance imaging. J Am Coll Cardiol 40:1856–1863. https://doi.org/10.1016/S0735-1097(02)02478-6

    Article  PubMed  Google Scholar 

  42. Sengupta P (2013) The laboratory rat: relating its age with human's. Int J Prev Med 4:624–630

    PubMed  PubMed Central  Google Scholar 

  43. Sicard D, Haak AJ, Choi KM, Craig AR, Fredenburgh LE, Tschumperlin DJ (2018) Aging and anatomical variations in lung tissue stiffness. Am J Physiol Lung Cell Mol Physiol 314:L946–L955. https://doi.org/10.1152/ajplung.00415.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tiscornia GC, Moretta R, Argenziano MA, Amorena CE, Garcia Gras EA (2014) Inhibition of connexin 43 in cardiac muscle during intense physical exercise. Scand J Med Sci Sports 24:336–344. https://doi.org/10.1111/sms.12017

    Article  CAS  PubMed  Google Scholar 

  45. van der Loo B, Labugger R, Skepper JN, Bachschmid M, Kilo J, Powell JM, Palacios-Callender M, Erusalimsky JD, Quaschning T, Malinski T, Gygi D, Ullrich V, Luscher TF (2000) Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192:1731–1744. https://doi.org/10.1084/jem.192.12.1731

    Article  PubMed  PubMed Central  Google Scholar 

  46. Vettor R, Valerio A, Ragni M, Trevellin E, Granzotto M, Olivieri M, Tedesco L, Ruocco C, Fossati A, Fabris R, Serra R, Carruba MO, Nisoli E (2014) Exercise training boosts eNOS-dependent mitochondrial biogenesis in mouse heart: role in adaptation of glucose metabolism. Am J Physiol Endocrinol Metab 306:E519–E528. https://doi.org/10.1152/ajpendo.00617.2013

    Article  CAS  PubMed  Google Scholar 

  47. Wang Y, Wisloff U, Kemi OJ (2010) Animal models in the study of exercise-induced cardiac hypertrophy. Physiol Res 59:633–644

    CAS  PubMed  Google Scholar 

  48. Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, Goldspink DF, Nadal-Ginard B, Torella D, Ellison GM (2014) The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. Eur Heart J 35:2722–2731. https://doi.org/10.1093/eurheartj/ehs338

    Article  CAS  PubMed  Google Scholar 

  49. Wisloff U, Ellingsen O, Kemi OJ (2009) High-intensity interval training to maximize cardiac benefits of exercise training? Exerc Sport Sci Rev 37:139–146. https://doi.org/10.1097/JES.0b013e3181aa65fc

    Article  PubMed  Google Scholar 

  50. Xiao J, Xu T, Li J, Lv D, Chen P, Zhou Q, Xu J (2014) Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells. Int J Clin Exp Pathol 7:663–669

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Celeste Resende for their assistance in sample preparation for morphological analysis.

Funding

This work was supported by the Portuguese Foundation for Science and Technology (FCT), European Union, QREN, and FEDER, and COMPETE funded the QOPNA research unit (project PEst-C/QUI/UI0062/2013), CIAFEL (UID/DTP/00617/2013), Unidade de Investigação Cardiovascular (UID/IC/00051/2013), iBiMED (UID/BIM/04501/2013), the research projects (EXPL/DTP-DES/1010/2013, FCOMP-01-0124-FEDER-041115, NETDIAMOND (SAICT-PAC/0047/2015)) and post-graduation students (grant numbers SFRH/BD/91067/2012 to R.N.F. and SFRH/BPD/90010/2012 to D.M.G.).

Author information

Authors and Affiliations

  1. Departamento de Cirurgia e Fisiologia, Faculdade de Medicina, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Rita Nogueira-Ferreira, Manuel Santos, Rui Vitorino & Daniel Moreira-Gonçalves

  2. QOPNA & LAQV, Departamento de Química, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Rita Ferreira & Ana Isabel Padrão

  3. CIAFEL, Faculdade de Desporto, Universidade do Porto, R. Dr. Plácido da Costa 91, 4200-450, Porto, Portugal

    Ana Isabel Padrão & Daniel Moreira-Gonçalves

  4. CITAB, Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, Quinta de Prados, 5001-911, Vila Real, Portugal

    Paula Oliveira

  5. School of Kinesiology, Auburn University, Auburn, AL, USA

    Andreas N. Kavazis

  6. iBiMED, Departamento de Ciências Médicas, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Rui Vitorino

Authors
  1. Rita Nogueira-Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rita Ferreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ana Isabel Padrão
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paula Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Manuel Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Andreas N. Kavazis
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rui Vitorino
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daniel Moreira-Gonçalves
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Rita Nogueira-Ferreira or Daniel Moreira-Gonçalves.

Ethics declarations

The experiments were approved by the local Ethics Committee for Animal Experimentation (license number 008961) and performed in accordance with European Parliament Directive 2010/63/EU

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Supplementary Fig. 1

Effect of exercise training on RAF-1 (74 kDa) in RV and LV and on RAF-1 and SIRT3 (28 kDa) content in isolated mitochondria. SED: sedentary, EX: exercise, LV: left ventricle, RV: right ventricle, RAF-1: RAF proto-oncogene serine/threonine-protein kinase, SIRT3: NAD-dependent deacetylase sirtuin-3. Representative immunoblots are shown above the correspondent graph (sample order has correspondence to the order of the groups presented in the graph). Values are presented as mean ± standard deviation (n = 4-6 per group). ***P < 0.001 vs. SED group. (PNG 175 kb)

High Resolution Image (TIF 271 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nogueira-Ferreira, R., Ferreira, R., Padrão, A.I. et al. One year of exercise training promotes distinct adaptations in right and left ventricle of female Sprague-Dawley rats. J Physiol Biochem 75, 561–572 (2019). https://doi.org/10.1007/s13105-019-00705-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-019-00705-4

Keywords

Search

Navigation