Moderate Continuous Aerobic Exercise Training Improves Cardiomyocyte Contractility in Β1 Adrenergic Receptor Knockout Mice

Abstract Background: The lack of cardiac β1-adrenergic receptors (β1-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 β1 adrenergic receptor knockout (β1ARKO) mice. Methods: Four- to five-month-old male wild type (WT) and β1ARKO mice were divided into groups: WT control (WTc) and trained (WTt); and β1ARKO control (β1ARKOc) and trained (β1ARKOt). 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 β1ARKO and exercised mice exhibited a higher (p < 0.05) running capacity than WT and sedentary ones, respectively. The β1ARKO 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 β1ARKO 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 β1ARKO mice. Conclusion: MCAE improves myocyte contractility in the left ventricle of β1ARKO mice. This is evidence to support the therapeutic value of this type of exercise training in the treatment of heart diseases involving β1-AR desensitization or reduction.

摘要 背景：心肌β1肾上腺素能受体(β1-adrenergic receptor, β1-AR)缺失会对心肌正性变力与正性变松弛的调控产生负面影响，长期可诱发心力衰竭(heart failure, HF)。目前中等强度有氧运动(moderate-intensity aerobic exercise, MCAE)被推荐作为心力衰竭患者的辅助治疗方案。
目的：探究中等强度有氧运动对β1肾上腺素能受体基因敲除(β1 adrenergic receptor knockout, β1ARKO)小鼠左心室(left ventricular, LV)心肌细胞收缩特性的影响。
方法：选取4~5月龄的雄性野生型(wild type, WT)及β1ARKO小鼠，分为四组：野生型对照组(WTc)、野生型训练组(WTt)；β1ARKO对照组(β1ARKOc)、β1ARKO训练组(β1ARKOt)。训练组小鼠在跑台上进行中等强度有氧运动训练，训练方案为每日60分钟，以最大速度的60%强度运动，每周5天，持续8周。所有比较均以P≤0.05作为差异具有统计学意义的判定标准。
结果：β1ARKO小鼠的跑步能力显著高于野生型对照组小鼠，运动训练组小鼠的跑步能力显著高于静坐对照组小鼠（P<0.05）。β1ARKO小鼠的体质量(body weight, BW)、心脏质量(heart weight, HW)、左心室质量(left ventricle weight, LVW)以及HW/BW与LVW/BW比值均高于野生型小鼠，但中等强度有氧运动未对上述体质量及脏器质量相关参数产生影响。β1ARKO小鼠的左心室心肌细胞收缩幅度、收缩速率及舒张速率均显著高于野生型小鼠（P<0.05）；此外，中等强度有氧运动可进一步提升β1ARKO小鼠心肌细胞的收缩幅度、收缩速率及舒张速率（P<0.05）。
结论：中等强度有氧运动可改善β1ARKO小鼠左心室心肌细胞的收缩功能。本研究结果为该类运动训练用于治疗β1-AR脱敏或表达降低相关心脏疾病提供了实验依据。