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Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension

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Abstract

Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.

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Acknowledgments

We are very thankful to Miss Celeste Resende, Marina Neto, Manuel Pinto, Cristine Schmidt, António Bovolini for their technical support with animal care, training protocols and tissue processing. We are also very grateful to Maria José Mendes and Antónia Teles for their valuable collaboration in the sample’s preparation for molecular biology analysis.

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Authors and Affiliations

  1. Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Daniel Moreira-Gonçalves, Nuno Moreno, Ana Filipa Silva, Francisco Vasques-Nóvoa, Nádia Gonçalves, Mário Santos, Adelino F. Leite-Moreira & Tiago Henriques-Coelho

  2. Centre of Physical Activity, Health and Leasure, Faculty of Sport, University of Porto, Rua Plácido Costa 91, 4200-450, Porto, Portugal

    Daniel Moreira-Gonçalves, Hélder Fonseca, Sara Vieira & José Alberto Duarte

  3. Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Adelino F. Leite-Moreira

  4. Department of Cardiothoracic Surgery, Hospital of São João, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal

    Adelino F. Leite-Moreira

  5. Department of Chemistry, Organic Chemistry, Natural and Agrofood Products, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Rita Ferreira, Ana Isabel Padrão & Francisco Amado

  6. Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal

    Rita Ferreira, Ana Isabel Padrão & Francisco Amado

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  1. Daniel Moreira-Gonçalves
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  2. Rita Ferreira
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Correspondence to Daniel Moreira-Gonçalves.

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This work was supported by Portuguese-Foundation-for-Science and-Technology grants PTDC/DES/104567/2008, PEst-C/SAU/UI0051/2014 and EXCL/BIMMEC/0055/2012 (partially funded by FEDER through COMPETE) and European-Commission grant FP7-Health-2010; MEDIA-261409. The Research Centre on Physical Activity Health and Leisure (CIAFEL) is supported by Pest-OE/SAU/UI0617/2011. Daniel Moreira-Gonçalves and Hélder Fonseca are supported by an individual grant from Portuguese-Foundation-for-Science and-Technology (SFRH/BPD/90010/2012 and SFRH/BPD/78259/2011, respectively).

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Moreira-Gonçalves, D., Ferreira, R., Fonseca, H. et al. Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension. Basic Res Cardiol 110, 57 (2015). https://doi.org/10.1007/s00395-015-0514-5

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