Apelin increases contractility in failing cardiac muscle
Apelin increases contractility in failing cardiac muscle
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DOI：
10.1016/j.ejphar.2006.09.034
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发表时间：
2006-12-28
影响因子：
5
通讯作者：
Gao, Wei Dong
中科院分区：
文献类型：
--
作者：
Dai, Tieying;Ramirez-Correa, Genaro;Gao, Wei Dong
Apelin是Apelin -angiotension receptor-like 1 （APJ）的一种配体，最近在正常心脏中被证明是一种有效的正性肌力剂。在人类中，apelin的水平在早期心力衰竭时上升，在晚期心力衰竭时下降。在本研究中，我们验证了apelin直接增强衰竭大鼠心肌收缩的假设。将大鼠暴露于缺氧（吸入10% O-2空气）14-16周，诱导继发性肺动脉高压右心室心力衰竭。将小梁解剖并安装在力传感器和机械臂之间，用Krebs-Henseleit （K-H）溶液（pH 7.4, 22℃）浸泡，并加载fura-2。与对照组相比，在Apelin-12（10类似于70 nM， [Ca2+](o) = 0.5 mM）的存在下，衰竭肌肉中的力发展和[Ca2+]瞬态振幅都以剂量依赖性的方式增加（70 nM时为36 +/- 7%比7.4 +/- 5%,P < 0.05）。与对照组相比，[Ca2+](i)瞬态增加了18.4 +/- 9.5% （4.5 1.9%,P < 0.05）。在外部Ca2+ (0.5-2.0 mM)范围内，apelin存在时收缩的增加也保持不变。衰竭肌肉的稳态力-[Ca2+](i)关系显示最大Ca2+激活力（F-max）降低（51.45 +/- 5.3 vs. 98.5 +/- 11.5 mN/mm(2), p < 0.001），最大激活（Ca-50）的50%所需的Ca2+没有变化（0.45 +/- 0.07 vs. 0.30 +/- 0.04 mu M, p > 0.05）和Hill系数（4.60 +/- 0.73 vs. 3.17 +/- 0.92, p > 0.05）。Apelin （70 nM）对衰竭肌肉的稳态力-[Ca2+]j关系没有影响(F-max: 63.03 +/- 3.5 mN/mm(2)；Ca-50: 0.50 +/- 0.08 μ M；希尔系数：4.73±0.89)。这些结果表明，apelin在衰竭心肌中发挥选择性的正性肌力作用，增加的力发展是增加[Ca2+](i)瞬态的结果，而不是肌丝钙反应性的变化。(c) 2006 Elsevier b.v.版权所有
Apelin, a ligand for apelin-angiotension receptor-like 1 (APJ), has recently been shown to be a potent positive inotropic agent in normal hearts. In humans, levels of apelin have been shown to rise in early-stage heart failure and to fall in late-stage heart failure. In this study, we tested the hypothesis that apelin augments contraction directly in failing rat cardiac muscle. Right ventricular heart failure secondary to pulmonary hypertension was induced by exposing the rats to hypoxia (10% O-2 inhaled air) for 14-16 weeks. Trabeculae were dissected and mounted between a force transducer and a motor arm, superfused with Krebs-Henseleit (K-H) solution (pH 7.4, 22 degrees C), and loaded with fura-2. Both force development and [Ca2+], transient amplitude increased in a dose-dependent manner in the presence of Apelin-12 (10 similar to 70 nM, [Ca2+](o) = 0.5 mM) in failing muscles as compared to control (36 +/- 7% vs. 7.4 +/- 5% at 70 nM, P < 0.05). Also, [Ca2+](i) transients increased up to 18.4 +/- 9.5% as compared to control (4.5 1.9%, P < 0.05). The increases in contraction in the presence of apelin were also maintained over a range of external Ca2+ (0.5-2.0 mM). Steady-state force-[Ca2+](i) relation of the failing muscles reveals decreased maximal Ca2+-activated force (F-max) (51.45 +/- 5.3 vs. 98.5 +/- 11.5 mN/mm(2), p < 0.001), with no Changes in Ca2+ required for 50% of maximal activation (Ca-50) (0.45 +/- 0.07 vs. 0.30 +/- 0.04 mu M, P > 0.05) and Hill coefficient (4.60 +/- 0.73 vs. 3.17 +/- 0.92, P > 0.05). Apelin (70 nM) had no effect on the steady-state force-[Ca2+]j relation in failing muscles (F-max: 63.03 +/- 3.5 mN/mm(2); Ca-50: 0.50 +/- 0.08 mu M; Hill coefficient: 4.73 +/- 0.89). These results indicate that apelin exerts a selective positive inotropic action in failing myocardium, The increased force development is the result of increased [Ca2+](i) transients rather than changes in myofilament calcium responsiveness. (c) 2006 Elsevier B.V All rights reserved.