Stones Rachel, Natali Antonio, Billeter Rudolf, Harrison Simon, White Ed
Institute of Membrane and Systems Biology, The University of Leeds, Leeds LS2 9JT, UK.
Exp Physiol. 2008 Sep;93(9):1065-75. doi: 10.1113/expphysiol.2008.042598. Epub 2008 May 16.
Regular exercise is beneficial to cardiovascular health. We tested whether mild voluntary exercise training modifies key myocardial parameters [ventricular mass, intracellular calcium ([Ca2+]i) handling and the response to beta-adrenoceptor (beta-AR) stimulation] in a manner distinct from that reported for beneficial, intensive training and pathological hypertrophic stimuli. Female rats performed voluntary wheel-running exercise for 6-7 weeks. The mRNA expression of target proteins was measured in left ventricular tissue using real-time reverse transcriptase-polymerase chain reaction. Simultaneous measurement of cell shortening and [Ca2+]i transients were made in single left ventricular myocytes and the inotropic response to beta1- and beta2-AR stimulation was measured. Voluntary exercise training resulted in cardiac hypertrophy, the heart weight to body weight ratio being significantly greater in trained compared with sedentary animals. However, voluntary exercise caused no significant alteration in the size or time course of myocyte shortening and [Ca2+]i transients or in the mRNA levels of key proteins that regulate Ca2+ handling. The positive inotropic response to beta1-AR stimulation and the level of beta1-AR mRNA were unaltered by voluntary exercise but both mRNA levels and inotropic response to beta2-AR stimulation were significantly reduced in trained animals. The beta2-AR inotropic response was restored by exposure to pertussis toxin. We propose that in contrast to pathological stimuli and to beneficial, intense exercise training, modulation of Ca2+ handling is not a major adaptive mechanism in the response to mild voluntary exercise. In addition, and in a reversal of the situation seen in heart failure, voluntary exercise training maintains the beta1-AR response but reduces the beta2-AR response. Therefore, although voluntary exercise induces cardiac hypertrophy, there are distinct differences between its effects on key myocardial regulatory mechanisms and those of hypertrophic stimuli that eventually cause cardiac decompensation.
规律运动有益于心血管健康。我们测试了轻度自主运动训练是否会以一种不同于有益的高强度训练和病理性肥大刺激所报道的方式，改变关键的心肌参数[心室质量、细胞内钙（[Ca2+]i）处理以及对β-肾上腺素能受体（β-AR）刺激的反应]。雌性大鼠进行了6至7周的自主轮转运动。使用实时逆转录聚合酶链反应在左心室组织中测量靶蛋白的mRNA表达。在单个左心室心肌细胞中同时测量细胞缩短和[Ca2+]i瞬变，并测量对β1-和β2-AR刺激的变力反应。自主运动训练导致心脏肥大，与久坐不动的动物相比，训练组动物的心脏重量与体重之比显著更高。然而，自主运动并未使心肌细胞缩短和[Ca2+]i瞬变的大小或时间进程，或调节Ca2+处理的关键蛋白的mRNA水平发生显著改变。自主运动并未改变对β1-AR刺激的正性变力反应和β1-AR mRNA水平，但训练组动物中对β2-AR刺激的mRNA水平和变力反应均显著降低。暴露于百日咳毒素可恢复β2-AR变力反应。我们提出，与病理性刺激和有益的高强度运动训练相反，Ca2+处理的调节不是对轻度自主运动反应中的主要适应性机制。此外，与心力衰竭中所见情况相反，自主运动训练维持了β1-AR反应，但降低了β2-AR反应。因此，尽管自主运动可诱导心脏肥大，但它对关键心肌调节机制的影响与最终导致心脏失代偿的肥大刺激的影响之间存在明显差异。
