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Alterations of β3-adrenoceptors expression and their myocardial functional effects in physiological model of chronic exercise-induced cardiac hypertrophy

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Abstract

Physical training induces cardiovascular autonomic nervous system regulation adaptations, which could result from β adrenergic receptor (AR) modifications. Among them, β3 AR alterations have been recently reported but their functional effect remained to discuss. To explain the β3 AR gene expression in relation to function, we simultaneously studied the left ventricle (LV) β3 AR mRNA and protein levels and the myocardial functional effects of a β3 AR agonist following physical training. Forty rats were assigned to either a control (C; N = 20) or a trained (T; N = 20) group. The treadmill running protocol was performed for 8 weeks. Histological measurements on LV slices were quantified. The β3 AR mRNA abundance was studied with RT-PCR and β3 AR protein density with Western-Blot analysis. Myocardial functional effects of a β3 AR agonist, BRL37344 (10−8 M), were studied in Langendorff-perfused hearts. Histological data confirmed the adapted patterns of the physiological cardiac hypertrophy observed in T (P < 0.01), with a significant increase in arteries density (P < 0.01) and an unchanged collagen concentration. The β3 AR protein density was increased in T (154 ± 38% in T vs. 100 ± 24% in C; P < 0.05), but no change was noted concerning the β3 AR mRNA level. After BRL37344 perfusion LVDP, +dP/dT and −dP/dT, in C (P < 0.01), and only +dP/dT in T (P < 0.05) were decreased. Moreover, all LV hemodynamic parameters were more altered after BRL37344 in C than in T (P < 0.01).

Thus, in this physiological model of cardiac hypertrophy, an increase of β3 AR density without β3 AR mRNA alteration was observed. Classical negative myocardial lusitropic and inotropic effects induced by a specific agonist of β3 AR were diminished in trained rats.

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Acknowledgements

We thank several people from the Faculty of Medicine, University of Rennes 1, Dr. M. Alizadeh, MD, (Laboratory of Histocompatibility and Immunogenetic) for his help concerning RT-PCR technique, Dr. F. Burtin, MD, Laboratory of Anatomopathology for her helpful advice concerning histological slides and Mr C. Mouas (INSERM U127, Lariboisière Hospital, Paris) for their technical support. We also thank Mr Gerald G. Pope PhD MD (Medical and Scientific translations), for his helpful advice for English translation. This work has been supported in part by a grant from the “Club des Cardiologues du Sport”.

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Authors and Affiliations

  1. EA 1274– Laboratory of Physiology and Biomechanics of Muscular Exercise, UFR-APS, University of Rennes 2, Av. Charles Tillon, Rennes Cedex, 35044, France

    J. Barbier & F. Rannou-Bekono

  2. EA 3194–Laboratory of Medical Physiology, University of Rennes 1, Faculty of Medicine, Av. Pr. Léon Bernard, Rennes Cedex, 35044, France

    J. Marchais & F. Carré

  3. JE 2426–Laboratory of Physiology of Exercise Cardiovascular Adaptations, UFR-Sciences, University of Avignon, Av. Louis Pasteur, Avignon Cedex, 84000, France

    S. Tanguy

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  1. J. Barbier
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  2. F. Rannou-Bekono
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  3. J. Marchais
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  4. S. Tanguy
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  5. F. Carré
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Correspondence to J. Barbier.

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Barbier, J., Rannou-Bekono, F., Marchais, J. et al. Alterations of β3-adrenoceptors expression and their myocardial functional effects in physiological model of chronic exercise-induced cardiac hypertrophy. Mol Cell Biochem 300, 69–75 (2007). https://doi.org/10.1007/s11010-006-9370-9

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  • DOI: https://doi.org/10.1007/s11010-006-9370-9

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