首页> 外文期刊>American Journal of Physiology >Microtubules modulate cardiomyocyte beta-adrenergic response in cardiac hypertrophy.
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Microtubules modulate cardiomyocyte beta-adrenergic response in cardiac hypertrophy.

机译:微管调节心脏肥大中的心肌β-肾上腺素能反应。

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The role of microtubules in modulating cardiomyocyte beta-adrenergic response was investigated in rats with cardiac hypertrophy. Male Sprague-Dawley rats underwent stenosis of the abdominal aorta (hypertensive, HT) or sham operation (normotensive, NT). Echocardiography and isolated left ventricular cardiomyocyte dimensions demonstrated cardiac hypertrophy in the HT rats after 30 wk. Cardiomyocyte microtubule fraction was assayed by high-speed centrifugation and Western blot. In contrast to previous reports of increased microtubules after acute pressure overload, microtubule fraction for HT was significantly lower than that for NT. Cardiomyocytes were exposed to either 1 microM colchicine, 10 microM taxol, or equivalent volume of vehicle. Colchicine decreased microtubules, and taxol increased microtubules in both groups. Cardiomyocyte cytosolic calcium ([Ca2+]c) and shortening/relaxation dynamics were assessed during exposure to increasing isoproterenol concentrations. The beta-adrenergic response for these variables in the HT group was blunted compared with NT. However, increased microtubule assembly by taxol partially recovered the normal beta-adrenergic response for time to peak [Ca2+]c, time to peak shortening, and mechanical relaxation variables. Microtubule assembly may play a significant role in determining cardiomyocyte beta-adrenergic response in chronic cardiac hypertrophy.
机译:在患有心肌肥大的大鼠中研究了微管在调节心肌β-肾上腺素能反应中的作用。雄性Sprague-Dawley大鼠经历了腹主动脉狭窄(高血压,HT)或假手术(血压正常,NT)。超声心动图和孤立的左心室心肌细胞的大小显示HT大鼠在30周后出现心脏肥大。通过高速离心和蛋白质印迹法测定心肌微管级分。与先前报道的急性压力超负荷后微管增加有关,HT的微管分数明显低于NT的微管分数。将心肌细胞暴露于1 microM秋水仙碱,10 microM紫杉醇或等体积的媒介物中。两组中秋水仙碱减少了微管,紫杉醇增加了微管。在暴露于增加的异丙肾上腺素浓度期间,评估了心肌细胞的胞质钙([Ca2 +] c)和缩短/松弛动力学。与NT相比,HT组中这些变量的β-肾上腺素反应迟钝。但是,紫杉醇增加的微管装配可部分恢复正常的β-肾上腺素反应,以达到[Ca2 +] c峰的时间,缩短峰的时间和机械弛豫变量。微管组装可能在确定慢性心脏肥大中的心肌β-肾上腺素反应中起重要作用。

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