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Role of the β3-adrenergic receptor subtype in catecholamine-induced myocardial remodeling

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Abstract

β3-Adrenoceptors (AR) stimulate cardiac Na+/K+ pump in healthy hearts. β3-ARs are upregulated by persistent sympathetic hyperactivity; however, their effect on Na+/K+ ATPase activity and ventricular function in this condition is still unknown. Here, we investigate preventive effects of additional β3-AR activation (BRL) on Na+/K+ ATPase activity and in vivo hemodynamics in a model of noradrenaline-induced hypertrophy. Rats received NA or NA plus simultaneously administered BRL in vivo infusion for 14 days; their cardiac function was investigated by left ventricular pressure–volume analysis. Moreover, fibrosis and apoptosis were also assessed histologically. NA induced an hypertrophic pattern, as detected by morphological, histological, and biochemical markers. Additional BRL exposure reversed the hypertrophic pattern and restored Na+/K+ ATPase activity. NA treatment increased systolic function and depressed diastolic function (slowed relaxation). Additional BRL treatment reversed most NA-induced hemodynamic changes. NA decreased Na+/K+ pump α2 subunit expression selectively, a change also reversed by additional BRL treatment. Increasing β3-AR stimulation may prevent the consequences of chronic NA exposure on Na+/K+ pump and in vivo hemodynamics. β3-AR agonism may thus represent a new therapeutic strategy for pharmacological modulation of hypertrophy under conditions of chronically enhanced sympathetic activity.

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Acknowledgements

This work was supported by Ankara University Scientific Research Projects Coordination Unit (Project Number: 13L3336008, 2015). Gizem Kayki Mutlu was a PhD fellow of Turkish Scientific and Technical Research Council (TUBITAK).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Ankara University, 06100, Tandogan, Ankara, Turkey

    Gizem Kayki Mutlu, Ebru Arioglu Inan & Irem Karaomerlioglu

  2. Department of Pharmacology, Faculty of Pharmacy, Bezmialem Vakif University, Fatih, 34093, Istanbul, Turkey

    V. Melih Altan

  3. Department of Histology and Embryology, Hacettepe University Faculty of Medicine, 06100, Sihhiye, Ankara, Turkey

    Nilgun Yersal & Petek Korkusuz

  4. Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano-Bicocca, Milan, Italy

    Marcella Rocchetti & Antonio Zaza

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  1. Gizem Kayki Mutlu
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Correspondence to Gizem Kayki Mutlu.

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Kayki Mutlu, G., Arioglu Inan, E., Karaomerlioglu, I. et al. Role of the β3-adrenergic receptor subtype in catecholamine-induced myocardial remodeling. Mol Cell Biochem 446, 149–160 (2018). https://doi.org/10.1007/s11010-018-3282-3

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