ABC | Volume 110, Nº3, March 2018

Original Article Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β 1 Adrenergic Receptor Knockout Mice Aurora Corrêa Rodrigues, 1 Antônio José Natali, 1 Daise Nunes Queiroz da Cunha, 1 Alexandre Jayme Lopes Dantas Costa, 1 Anselmo Gomes de Moura, 1 Miguel Araújo Carneiro-Júnior, 1 Leonardo Bonato Félix, 1 Patrícia Chakur Brum, 2 Thales Nicolau Prímola-Gomes 1 Universidade Federal de Viçosa (UFV), Viçosa, MG – Brazil 1 Universidade de São Paulo (USP), São Paulo, SP – Brazil 2 Mailing Address: Thales Nicolau Prímola Gomes • Universidade Federal de Vi osa - Departamento de Educa ão Física - Av. Ph. Rolfs, s/n. Postal Code 36570-000, Campus Universitário, Vi osa, MG – Brazil E-mail: thales.gomes@ufv.br , thalesprimola@gmail.com Manuscript received May 14, 2017, revised manuscript September 15, 2017, accepted Septeber 22, 2017 DOI: 10.5935/abc.20180025 Abstract Background: The lack of cardiac β 1 -adrenergic receptors ( β 1 -AR) negatively affects the regulation of both cardiac inotropy and lusitropy, leading, in the long term, to heart failure (HF). Moderate-intensity aerobic exercise (MCAE) is recommended as an adjunctive therapy for patients with HF. Objective: We tested the effects of MCAE on the contractile properties of left ventricular (LV) myocytes from β 1 adrenergic receptor knockout ( β 1 ARKO) mice. Methods: Four- to five-month-old male wild type (WT) and β 1 ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β 1 ARKO control ( β 1 ARKOc) and trained ( β 1 ARKOt). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. P ≤ 0.05 was considered significant in all comparisons. Results: The β 1 ARKOand exercisedmice exhibited a higher (p<0.05) running capacity thanWT and sedentary ones, respectively. The β 1 ARKO mice showed higher body (BW), heart (HW) and left ventricle (LVW) weights, as well as the HW/BW and LVW/BW than WT mice. However, the MCAE did not affect these parameters. Left ventricular myocytes from β 1 ARKO mice showed increased (p < 0.05) amplitude and velocities of contraction and relaxation than those from WT. In addition, MCAE increased (p < 0.05) amplitude and velocities of contraction and relaxation in β 1 ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β 1 ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β 1 -AR desensitization or reduction. (Arq Bras Cardiol. 2018; 110(3):256-262) Keywords: Heart Failure; Exercise; Myocardial Contraction; Myocytes, Cardiac; Adrenergic beta 1 Receptor Antagonists; Mice. Introduction Chronic sympathetic hyperactivity resulting from altered autonomic nervous system balance is common in many cardiovascular disease states, ending up in heart failure (HF), and is related to a higher incidence of morbidity and mortality. 1,2 Such hyperactivity is paralleled by a decrease in β -adrenergic receptors ( β -AR) density and desensitization of the remaining β -AR, thus leading to a reduced cardiac contractile response to β -AR activation. 3 In this framework, β 1 -AR, predominant in the heart, is selectively reduced, resulting in a modified ratio of β 1 to β 2 subtypes, 4 and β 2 -AR are markedly coupled to inhibitory G protein. Consequently, inasmuch as the β 1 -AR phosphorylates several Ca 2+ regulatory proteins involved in cardiomyocyte excitation-contraction coupling, 5-7 cardiac chronotropism, inotropism and lusitropism are impaired under adrenergic stimulation. 8 Exercise training in cardiac rehabilitation is very important in several cardiovascular diseases, including chronic HF. 9 Continuous moderate-intensity aerobic exercise (MCAE) is, at present, the best-established form of exercise for this population because of its efficacy and safety. 10 For example, aerobic exercise training recovers the resting autonomic balance in HF patients by reducing the resting sympathetic nerve activity, 11 and restoring the parasympathetic tone to the heart. 12,13 In the myocardium, aerobic exercise training increases stroke volume and, hence, cardiac output in patients 14,15 and in animal models of HF, 8 although some studies failed to confirm such benefits. 11,12 At the cellular level, studies on animal models for sympathetic hyperactivity have demonstrated aerobic exercise training improves the net balance of cardiac Ca 2+ handling proteins either alone 8,16 or in combination with β -blockers. 17 Nevertheless, whether MCAE training affects mechanical properties of single myocytes in a heart lacking β 1 -AR remains to be elucidated. Therefore, the aim of this study was to test the effects of an MCAE program on mechanical properties of single 256