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Angiotensin II Type 2 Receptor (AT2R) is Associated with Increased Tolerance of the Hyperthyroid Heart to Ischemia-Reperfusion

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Abstract

Background

Thyroid hormone induces cardiac hypertrophy and preconditions the myocardium against Ischemia/Reperfusion (I/R) injury. Type 2 Angiotensin II receptors (AT2R) are shown to be upregulated in cardiac hypertrophy observed in hyperthyroidism and this receptor has been reported to mediate cardioprotection against ischemic injury.

Methods

The aim of the present study was to evaluate the role of AT2R in the recovery of myocardium after I/R in isolated hearts from T3 treated rats. Male Wistar rats were treated with triiodothyronine (T3; 7 μg/100 g BW/day, i.p.) in the presence or not of a specific AT2R blocker (PD123,319; 10 mg/Kg) for 14 days, while normal rats served as control. After treatment, isolated hearts were perfused in Langendorff mode; after 30 min of stabilization, hearts were subjected to 20 min of zero-flow global ischemia followed by 25 min, 35 min and 45 min of reperfusion.

Results

T3 treatment induced cardiac hypertrophy, which was not changed by PD treatment. Post-ischemic recovery of cardiac function was increased in T3-treated hearts after 35 min and 45 min of reperfusion as compared to control and the ischemic contracture was accelerated and intensified. AT2R blockade was able to return the evaluated functional parameters of cardiac performance (LVDP, +dP/dtmáx and −dP/dtmin) to the control condition. Furthermore, AT2R blockade prevented the increase in AMPK expression levels induced by T3, suggesting its possible involvement in this process.

Conclusion

AT2R plays a significant role in T3-induced cardioprotection.

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Acknowledgments

FM Tavares and IB da Silva contributed equally to this work.

We thank Dr. DaltonVassalo from Department of Physiology, University of Espirito Santo, Brazil, for the contribution with numerous suggestions during this study.

This study received financial support in the form of grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, Foundation for the Support of Research in the State of Sao Paulo) and ConselhoNacional de DesenvolvimentoCientífico e Tecnológico (CNPq, National Council for Scientific and Technological Development).

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Cell Biology and Functional Anatomy, Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 2415, São Paulo, SP, 05508-900, Brazil

    Felix Meira Tavares, Ivson Bezerra da Silva, Dayane Aparecida Gomes & Maria Luiza Morais Barreto-Chaves

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  1. Felix Meira Tavares
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  2. Ivson Bezerra da Silva
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  3. Dayane Aparecida Gomes
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  4. Maria Luiza Morais Barreto-Chaves
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Correspondence to Maria Luiza Morais Barreto-Chaves.

Additional information

Felix Meira Tavares and Ivson Bezerra da Silva contributed equally to this work.

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Tavares, F.M., da Silva, I.B., Gomes, D.A. et al. Angiotensin II Type 2 Receptor (AT2R) is Associated with Increased Tolerance of the Hyperthyroid Heart to Ischemia-Reperfusion. Cardiovasc Drugs Ther 27, 393–402 (2013). https://doi.org/10.1007/s10557-013-6473-x

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