Geenen D L, Malhotra A, Scheuer J, Buttrick P M
Cardiology Division, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Mol Cell Cardiol. 1997 Oct;29(10):2711-6. doi: 10.1006/jmcc.1997.0502.
To assess the role of intermittent beta-adrenergic stimulation on alpha-myosin heavy chain expression and cellular hypertrophy, we studied the effect of intermittent dobutamine on myosin heavy chain isoform distribution and protein synthesis in the heterotopic rat heart preparation. This model allows the analysis of a pharmocologic stimulus in isolation from the mechanical load on the myocardium induced by the drug. Intermittent administration of dobutamine resulted in elevated alpha-MHC levels (75 +/- 12%) compared to control (55 +/- 10%; X +/- s.e.; P<0.05) transplanted hearts. This effect was not altered by alpha-receptor blockade with terazosin (72 +/- 8%). Intermittently pacing the transplanted hearts at the same rate as observed with dobutamine alone, also elevated alpha-MHC levels (70 +/- 5%). In contrast, total protein synthesis in the transplanted hearts was not altered with any of the drug or pacing interventions compared to control hearts. These data suggest that intermittent beta-receptor stimulation and/or intermittent increased heart rate contribute to altered patterns of myosin heavy chain expression. However, increases in cardiac mass and protein synthesis are probably mediated by hemodynamic factors rather than catecholamine stimulation.
为评估间歇性β-肾上腺素能刺激对α-肌球蛋白重链表达和细胞肥大的作用,我们研究了间歇性多巴酚丁胺对异位大鼠心脏标本中肌球蛋白重链异构体分布和蛋白质合成的影响。该模型可在不考虑药物对心肌机械负荷影响的情况下,单独分析药物刺激作用。与对照(55±10%;均值±标准误;P<0.05)移植心脏相比,间歇性给予多巴酚丁胺可使α-MHC水平升高(75±12%)。用特拉唑嗪进行α-受体阻断并未改变这一效应(72±8%)。以与单独使用多巴酚丁胺时相同的频率对移植心脏进行间歇性起搏,也可使α-MHC水平升高(70±5%)。相比之下,与对照心脏相比,移植心脏中的总蛋白质合成并未因任何药物或起搏干预而改变。这些数据表明,间歇性β-受体刺激和/或间歇性心率增加会导致肌球蛋白重链表达模式改变。然而,心脏质量和蛋白质合成的增加可能是由血流动力学因素介导的,而非儿茶酚胺刺激。