Publication:
Role of the beta(3)-adrenergic receptor subtype in catecholamine-induced myocardial remodeling

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2018-09-01
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Mutlu, Gizem Kayki
Inan, Ebru Arioglu
Karaomerlioglu, Irem
Altan, VECDİ MELİH
YERSAL, NİLGÜN
KORKUSUZ, PETEK
Rocchetti, Marcella
Zaza, Antonio
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Abstract
beta(3)-Adrenoceptors (AR) stimulate cardiac Na+/K+ pump in healthy hearts. beta(3)-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 beta(3)-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 alpha 2 subunit expression selectively, a change also reversed by additional BRL treatment. Increasing beta(3)-AR stimulation may prevent the consequences of chronic NA exposure on Na+/K+ pump and in vivo hemodynamics. beta(3)-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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Mutlu G. K. , Inan E. A. , Karaomerlioglu I., Altan V. M. , YERSAL N., KORKUSUZ P., Rocchetti M., Zaza A., -Role of the beta(3)-adrenergic receptor subtype in catecholamine-induced myocardial remodeling-, MOLECULAR AND CELLULAR BIOCHEMISTRY, cilt.446, ss.149-160, 2018
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