Chronic intermittent hypobaric hypoxia decreases β-adrenoceptor activity in right ventricular papillary muscle
Chronic intermittent hypobaric hypoxia decreases β-adrenoceptor activity in right ventricular papillary muscle
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DOI：
10.1152/ajpheart.00410.2009
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发表时间：
2010-04-01
影响因子：
4.8
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Guan, Yue;Gao, Lu;Zhang, Yi
关毅，高立，马宏，李勤，张宏，袁芳，周忠，张毅。慢性间歇性低压缺氧降低右心室乳头肌β-肾上腺素能受体活性。Am J Physiol Heart Circ Physiol 298：H1267-H1272，2010.首次发表于January 22，2010; doi：10.1152/ajpheart.00410.2009.慢性间歇性低压缺氧（CIHH）对缺血再灌注损伤具有有效的心脏保护作用。然而，其潜在机制尚不完全清楚。研究表明，阻断β-肾上腺素能受体可发挥抗心肌缺血作用并改善缺血心肌的心脏重塑。因此，我们确定了CIHH对大鼠右心室乳头肌β-肾上腺素能受体活性的影响。结果发现CIHH大鼠右心室乳头肌动作电位时程明显长于对照组。DL-异丙肾上腺素激活β-肾上腺素能受体可剂量依赖性地增加右心室乳头肌动作电位时程和收缩力。在CIHH大鼠，DL-异丙肾上腺素对动作电位时程的延长作用和正性肌力作用均明显低于对照组。放射性配体结合实验显示，CIHH大鼠右心室心肌β-肾上腺素能受体的密度和亲和力显著降低。此外，Western blot分析显示，CIHH大鼠心肌中的膜结合G蛋白G（s）α表达水平显著低于对照组大鼠。总的来说，这些数据表明CIHH通过降低受体密度和亲和力以及膜结合G（s）α抑制右心室乳头肌中的β-肾上腺素能受体作用。这一机制可能与CIHH的心脏保护作用有关。
Guan Y, Gao L, Ma H, Li Q, Zhang H, Yuan F, Zhou Z, Zhang Y. Chronic intermittent hypobaric hypoxia decreases beta-adrenoceptor activity in right ventricular papillary muscle. Am J Physiol Heart Circ Physiol 298: H1267-H1272, 2010. First published January 22, 2010; doi: 10.1152/ajpheart.00410.2009.Chronic intermittent hypobaric hypoxia (CIHH) has an effective cardiac protection against ischemia-reperfusion injury. However, the underlying mechanisms are not fully known. It has been shown that blockade of beta-adrenergic receptor exerts anti-arrhythmic action and improves cardiac remodeling in ischemic myocardium. Thus we determined the influence of CIHH on beta-adrenergic receptor activity in right ventricular papillary muscle of rats. We found that the action potential duration in right ventricular papillary muscle was significantly longer in CIHH rats than in control rats. Activation of beta-adrenergic receptor with DL-isoproterenol dose-dependently increased action potential duration and the contractility in right ventricular papillary muscle. In CIHH rats, the prolonged effect of DL-isoproterenol on action potential duration and the positive inotropic effect were significantly decreased compared with that in control rats. Furthermore, radioligand-binding experiments revealed that the density and affinity of beta-adrenergic receptor in right ventricular myocardium was significantly lower in CIHH rats. In addition, Western blot analysis revealed that the membrane-bound G protein G(s)alpha expression level in cardiac myocardium was significantly lower in CIHH rats than that in control rats. Collectively, these data suggest that CIHH suppresses beta-adrenergic receptor action in right ventricular papillary muscle through decreasing receptor density and affinity, as well as membrane-bound G(s)alpha. This mechanism may be involved in the cardiac protective effect of CIHH.