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Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice

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Abstract

The role of exercise training (ET) on cardiac renin-angiotensin system (RAS) was investigated in 3–5 month-old mice lacking α2A- and α2C-adrenoceptors (α2A/α2CARKO) that present heart failure (HF) and wild type control (WT). ET consisted of 8-week running sessions of 60 min, 5 days/week. In addition, exercise tolerance, cardiac structural and function analysis were made. At 3 months, fractional shortening and exercise tolerance were similar between groups. At 5 months, α2A/α2CARKO mice displayed ventricular dysfunction and fibrosis associated with increased cardiac angiotensin (Ang) II levels (2.9-fold) and increased local angiotensin-converting enzyme activity (ACE 18%). ET decreased α2A/α2CARKO cardiac Ang II levels and ACE activity to age-matched untrained WT mice levels while increased ACE2 expression and prevented exercise intolerance and ventricular dysfunction with little impact on cardiac remodeling. Altogether, these data provide evidence that reduced cardiac RAS explains, at least in part, the beneficial effects of ET on cardiac function in a genetic model of HF.

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Acknowledgments

The authors want to thank the Fundação de Amparo à Pesquisa do Estado de São Paulo, São Paulo—SP (FAPESP # 2005/59740-7) for funding this present investigation. We also want to express our gratitude to Fundação Zerbini, São Paulo—SP, for the support in this study. M.G.P. holds scholarship from FAPESP (# 2006/57164-1). P.C.B. holds scholarship from Conselho Nacional de Pesquisa e Desenvolvimento—Brasil (CNPq, BPQ).

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Authors and Affiliations

  1. School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil

    M. G. Pereira, J. C. B. Ferreira, C. R. Bueno Jr, K. C. Mattos, E. M. Oliveira & Patricia Chakur Brum

  2. Heart Institute (InCor), Medical School, University of Sao Paulo, Sao Paulo, Brazil

    K. T. Rosa, M. C. Irigoyen & J. E. Krieger

  3. Departamento de Biodinâmica do Movimento do Corpo Humano, Escola de Educação Física e Esporte da Universidade de São Paulo, Av. Professor Mello Moraes, 65, Butantã, São Paulo, SP, CEP 05508-900, Brazil

    Patricia Chakur Brum

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  1. M. G. Pereira
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  2. J. C. B. Ferreira
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  3. C. R. Bueno Jr
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  4. K. C. Mattos
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  6. M. C. Irigoyen
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  7. E. M. Oliveira
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  9. Patricia Chakur Brum
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Correspondence to Patricia Chakur Brum.

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Pereira, M.G., Ferreira, J.C.B., Bueno, C.R. et al. Exercise training reduces cardiac angiotensin II levels and prevents cardiac dysfunction in a genetic model of sympathetic hyperactivity-induced heart failure in mice. Eur J Appl Physiol 105, 843–850 (2009). https://doi.org/10.1007/s00421-008-0967-4

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  • DOI: https://doi.org/10.1007/s00421-008-0967-4

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