Helwig Bryan, Schreurs Katherine M, Hansen Joslyn, Hageman K Sue, Zbreski Michael G, McAllister Richard M, Mitchell Kathy E, Musch Timothy I
Department of Anatomy and Physiology, Kansas State University, Manhattan, Kansas 66506-5802, USA.
J Appl Physiol (1985). 2003 Jun;94(6):2225-36. doi: 10.1152/japplphysiol.00279.2002. Epub 2003 Jan 31.
The mechanisms responsible for the decrements in exercise performance in chronic heart failure (CHF) remain poorly understood, but it has been suggested that sarcolemmal alterations could contribute to the early onset of muscular fatigue. Previously, our laboratory demonstrated that the maximal number of ouabain binding sites (B(max)) is reduced in the skeletal muscle of rats with CHF (Musch TI, Wolfram S, Hageman KS, and Pickar JG. J Appl Physiol 92: 2326-2334, 2002). These reductions may coincide with changes in the Na(+)-K(+)-ATPase isoform (alpha and beta) expression. In the present study, we tested the hypothesis that reductions in B(max) would coincide with alterations in the alpha- and beta-subunit expression of the sarcolemmal Na(+)-K(+)-ATPase of rats with CHF. Moreover, we tested the hypothesis that exercise training would increase B(max) along with producing significant changes in alpha- and beta-subunit expression. Rats underwent a sham operation (sham; n = 10) or a surgically induced myocardial infarction followed by random assignment to either a control (MI; n = 16) or exercise training group (MI-T; n = 16). The MI-T rats performed exercise training (ET) for 6-8 wk. Hemodynamic indexes demonstrated that MI and MI-T rats suffered from severe left ventricular dysfunction and congestive CHF. Maximal oxygen uptake (Vo(2 max)) and endurance capacity (run time to fatigue) were reduced in MI rats compared with sham. B(max) in the soleus and plantaris muscles and the expression of the alpha(2)-isoform of the Na(+)-K(+)-ATPase in the red portion of the gastrocnemius (gastrocnemius(red)) muscle were reduced in MI rats. After ET, Vo(2 max) and run time to fatigue were increased in the MI-T group of rats. This coincided with increases in soleus and plantaris B(max) and the expression of the alpha(2)-isoform in the gastrocnemius(red) muscle. In addition, the expression of the beta(2)-isoform of the gastrocnemius(red) muscle was increased in the MI-T rats compared with their sedentary counterparts. This study demonstrates that CHF-induced alterations in skeletal muscle Na(+)-K(+)-ATPase, including B(max) and isoform expression, can be partially reversed by ET.
慢性心力衰竭（CHF）中运动能力下降的机制仍未完全明确，但有研究表明肌膜改变可能是肌肉疲劳早期发作的原因。此前，我们实验室发现CHF大鼠骨骼肌中哇巴因结合位点的最大数量（B(max)）减少（Musch TI、Wolfram S、Hageman KS和Pickar JG。《应用生理学杂志》92: 2326 - 2334，2002年）。这些减少可能与钠钾ATP酶同工型（α和β）表达的变化同时出现。在本研究中，我们检验了以下假设：CHF大鼠中B(max)的减少与肌膜钠钾ATP酶α和β亚基表达的改变同时出现。此外，我们还检验了以下假设：运动训练会增加B(max)，同时使α和β亚基表达产生显著变化。大鼠接受假手术（假手术组；n = 10）或手术诱导心肌梗死，随后随机分为对照组（MI组；n = 16）或运动训练组（MI - T组；n = 16）。MI - T组大鼠进行6 - 8周的运动训练（ET）。血流动力学指标显示，MI组和MI - T组大鼠存在严重的左心室功能障碍和充血性CHF。与假手术组相比，MI组大鼠的最大摄氧量（Vo(2 max)）和耐力（疲劳奔跑时间）降低。MI组大鼠比目鱼肌和跖肌的B(max)以及腓肠肌红色部分（腓肠肌(红色)）钠钾ATP酶α(2)同工型的表达降低。运动训练后，MI - T组大鼠的Vo(2 max)和疲劳奔跑时间增加。这与比目鱼肌和跖肌B(max)的增加以及腓肠肌(红色)肌中α(2)同工型表达的增加同时出现。此外，与久坐不动的MI - T组大鼠相比，其腓肠肌(红色)肌中β(2)同工型的表达增加。本研究表明，CHF引起的骨骼肌钠钾ATP酶改变，包括B(max)和同工型表达，可通过运动训练部分逆转。
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