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Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice.

机译:生长激素和IGF-I对小鼠心脏肥大和基因表达的影响。

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Cardiac hypertrophic and contractile responses were studied in mice administered growth hormone (GH) and insulin-like growth factor (IGF-I) (8 mg . kg-1 . day-1), alone or in combination (IGF-I/GH), for 2 wk. Also, changes in expression of selected left ventricular (LV) genes in response to IGF-I/GH were compared with those in other forms of cardiac hypertrophy. GH or IGF-I alone at three to four times the usual dose in rats failed to produce increases in heart and LV weights and hemodynamic effects; however, IGF-I/GH was synergistic, increasing body weight and LV weights by 39 and 35%, respectively. A measure of myocardial contractility (maximal first derivative of LV pressure, catheter-tip micromanometry) was increased by 34% in the IGF/GH group, related in part to a force-frequency effect, since the heart rate increased by 21%. Other mice were treated surgically to produce pressure overload (transverse aortic constriction) or volume overload (arteriovenous fistula) for 2 wk; LV weights were then matched to those in the IGF-I/GH group, and mRNA levels of selected markers were assessed. In contrast to the increased mRNA levels of atrial natriuretic factor, alpha-skeletal actin, and collagen III generally observed in overloaded hearts, changes in IGF-I/GH-treated mice were not significant. Thus high-dose IGF-I/GH produce cardiac hypertrophy and a positive inotropic effect without causing significant changes in expression of fetal and other selected myocardial genes, suggesting that this hypertrophy may be of a more physiological type than that due to mechanical overload.
机译:在单独或联合给予生长激素(GH)和胰岛素样生长因子(IGF-1)(8 mg。kg-1。day-1)的小鼠中研究了心脏的肥大和收缩反应,持续2周。而且,将响应IGF-I / GH的所选左心室(LV)基因表达的变化与其他形式的心脏肥大进行了比较。在大鼠中,普通剂量的GH或IGF-I的剂量是普通剂量的三到四倍,但并不能增加心脏和左心室的重量以及血液动力学效应。但是,IGF-I / GH具有协同作用,使体重和左室重量分别增加了39%和35%。 IGF / GH组的心肌收缩力(LV压力的最大一阶导数,导管尖端显微测压)增加了34%,这部分与心率频率效应有关,因为心率增加了21%。对其他小鼠进行手术治疗,使其产生压力超负荷(横向主动脉狭窄)或体积超负荷(动静脉瘘),持续2周。然后将LV重量与IGF-I / GH组的重量相匹配,并评估所选标志物的mRNA水平。与在超负荷心脏中通常观察到的心钠素,α-骨骼肌肌动蛋白和胶原蛋白III的mRNA水平升高相反,经IGF-I / GH处理的小鼠的变化并不明显。因此,大剂量IGF-I / GH产生心脏肥大和正性肌力作用,而不会引起胎儿和其他选定的心肌基因表达的显着变化,这表明该肥大的生理类型可能比由于机械超负荷引起的生理类型更为严重。

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