Carneiro-Júnior M A, Quintão-Júnior J F, Drummond L R, Lavorato V N, Drummond F R, Amadeu M A, Oliveira E M, Felix L B, Cruz J S, Mill J G, Natali A J, Prímola-Gomes T N
Departamento de Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
Laboratório de Biologia do Exercício, Departamento de Educação Física, Universidade Federal de Viçosa, Viçosa, MG, Brasil.
Braz J Med Biol Res. 2014 Nov;47(11):960-5. doi: 10.1590/1414-431X20144063. Epub 2014 Aug 29.
In cardiomyocytes, calcium (Ca²⁺) release units comprise clusters of intracellular Ca²⁺ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca²⁺ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca²⁺ sparks (HC=7.61 ± 0.26 vs NC=4.79 ± 0.19 per 100 µm/s) and decreased its amplitude (HC=0.260 ± 0.08 vs NC=0.324 ± 0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05 ± 0.08 vs NC=1.26 ± 0.01 µm), total duration (HC=11.51 ± 0.12 vs NC=14.97 ± 0.24 ms), time to peak (HC=4.84 ± 0.06 vs NC=6.31 ± 0.14 ms), and time constant of decay (HC=8.68 ± 0.12 vs NC=10.21 ± 0.22 ms). These changes were partially reversed in HT rats (frequency of Ca²⁺ sparks=6.26 ± 0.19 µm/s, amplitude=0.282 ± 0.10 ΔF/F0, full width at half-maximum amplitude=1.14 ± 0.01 µm, total duration=13.34 ± 0.17 ms, time to peak=5.43 ± 0.08 ms, and time constant of decay=9.43 ± 0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes.
在心肌细胞中，钙（Ca²⁺）释放单元由位于肌浆网上的细胞内Ca²⁺释放通道簇组成，高血压是钙释放单元功能缺陷的一个公认原因。我们的目的是确定耐力运动训练是否可以减轻高血压对自发性高血压大鼠左心室心肌细胞中钙释放单元成分和Ca²⁺闪烁的有害影响。雄性Wistar大鼠和自发性高血压大鼠（4月龄）被分为4组：正常血压组（NC）和高血压对照组（HC），以及正常血压训练组（NT）和高血压训练组（HT）（每组7只大鼠）。NC组和HC组大鼠接受低强度跑步机跑步方案（每周5天，每天1小时，坡度为0%，最大跑步速度的50 - 60%），持续8周。与NC组大鼠相比，HC组大鼠中2型兰尼碱受体（RyR2）和FK506结合蛋白（FKBP12.6）的基因表达分别增加了（270%）和减少了（88%）。耐力运动训练通过降低RyR2（230%）和使FKBP12.6基因表达正常化（112%）逆转了这些变化。高血压还增加了Ca²⁺闪烁的频率（HC = 7.61 ± 0.26 vs NC = 4.79 ± 0.19次/100 µm/s），并降低了其幅度（HC = 0.260 ± 0.08 vs NC = 0.324 ± 0.10 ΔF/F0）、半最大幅度处的全宽（HC = 1.05 ± 0.08 vs NC = 1.26 ± 0.01 µm）、总持续时间（HC = 11.5 ± 0.12 vs NC = 14.97 ± 0.24 ms）、达到峰值的时间（HC = 4.84 ± 0.06 vs NC = 6.31 ± 0.14 ms）以及衰减时间常数（HC = 8.68 ± 0.12 vs NC = 10.21 ± 0.22 ms）。这些变化在HT组大鼠中部分得到逆转（Ca²⁺闪烁频率 = 6.26 ± 0.19 µm/s，幅度 = 0.282 ± 0.10 ΔF/F0，半最大幅度处的全宽 = 1.14 ± 0.01 µm，总持续时间 = 13.34 ± 0.17 ms，达到峰值的时间 = 5.43 ± 0.08 ms，衰减时间常数 = 9.43 ± 0.15 ms）。耐力运动训练减轻了高血压对左心室心肌细胞钙释放单元的有害影响。
