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Blockage of Angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation

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Abstract

Although most of effects of Angiotensin II (Ang II) related to cardiac remodelling can be attributed to type 1 Ang II receptor (AT1R), the type 2 receptor (AT2R) has been shown to be involved in the development of some cardiac hypertrophy models. In the present study, we investigated whether the thyroid hormone (TH) action leading to cardiac hypertrophy is also mediated by increased Ang II levels or by change on AT1R and AT2R expression, which could contribute to this effect. In addition, we also evaluated the possible contribution of AT2R in the activation of Akt and in the development of TH-induced cardiac hypertrophy. To address these questions, Wistar rats were treated with thyroxine (T4, 0.1 mg/kg BW/day, i.p.), with or without AT2R blocker (PD123319), for 14 days. Cardiac hypertrophy was identified based on heart/body weight ratio and confirmed by analysis of atrial natriuretic factor mRNA expression. Cardiomyocyte cultures were used to exclude the influence of TH-related hemodynamic effects. Our results demonstrate that the cardiac Ang II levels were significantly increased (80%, P < 0.001) as well as the AT2R expression (50%, P < 0.05) in TH-induced cardiac hypertrophy. The critical involvement of AT2R to the development of this cardiac hypertrophy in vivo was evidenced after administration of AT2 blocker, which was able to prevent in 40% (P < 0.01) the cardiac mass gain and the Akt activation induced by TH. The role of AT2R to the TH-induced cardiomyocyte hypertrophy was also confirmed after using PD123319 in the in vitro studies. These findings improve understanding of the cardiac hypertrophy observed in hyperthyroidism and provide new insights into the generation of future therapeutic strategies.

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Acknowledgments

This study received financial support in the form of grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of São Paulo; grant nos. 01/11678-8 and 03/04638-8) and from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, National Council for Scientific and Technological Development).

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Authors and Affiliations

  1. Laboratório de Biologia Celular e Anatomia Funcional, Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes 2415, Cidade Universitária, São Paulo, SP, 05508-900, Brazil

    G. P. Diniz & M. L. M. Barreto-Chaves

  2. Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil

    M. S. Carneiro-Ramos

  3. Natural and Human Sciences Center, Federal University of ABC, Santo André, Brazil

    M. S. Carneiro-Ramos

  4. Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil

    A. P. Nadu, J. Almeida, R. L. P. Vieira & R. A. S. Santos

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  1. M. S. Carneiro-Ramos
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  2. G. P. Diniz
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  3. A. P. Nadu
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  4. J. Almeida
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  5. R. L. P. Vieira
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  6. R. A. S. Santos
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  7. M. L. M. Barreto-Chaves
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Correspondence to M. L. M. Barreto-Chaves.

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Carneiro-Ramos, M.S., Diniz, G.P., Nadu, A.P. et al. Blockage of Angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation. Basic Res Cardiol 105, 325–335 (2010). https://doi.org/10.1007/s00395-010-0089-0

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  • DOI: https://doi.org/10.1007/s00395-010-0089-0

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