Adenosine A1 receptor activation reduces reactive oxygen species and attenuates stunning in ventricular myocytes.

Adenosine A1 receptor activation reduces reactive oxygen species and attenuates stunning in ventricular myocytes.
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腺苷 A1 受体激活可减少活性氧并减弱心室肌细胞的击晕作用。

DOI:
10.1006/jmcc.2000.1282
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发表时间:
2001
影响因子:
5
通讯作者:
Lasley,RD
Lasley,RD
中科院分区:
医学2区
文献类型:
--
作者:
Narayan,P;MentzerJr,RM;Lasley,RD

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短暂缺血或缺氧后活性氧(ROS)的形成被认为是心肌顿抑的根本原因。缺血/缺氧前腺苷A1受体激活可减轻顿抑,但其作用机制尚不清楚。加载ROS敏感性指示剂二氯荧光素的分离的大鼠心室肌细胞进行30分钟无葡萄糖缺氧,然后复氧。细胞内ROS增加175%(从缺氧前的水平)在复氧,而细胞缩短减少50%。在用腺苷A1激动剂2-氯- N6-环戊腺苷(CCPA)预处理的心肌细胞中,再氧诱导的ROS形成减弱了40%,顿抑减弱了50%(与未处理的心肌细胞相比)。线粒体KATP通道开放剂二氮嗪模拟了CCPA的作用。用线粒体ATP通道阻断剂5-羟基癸酸酯或非选择性ATP通道阻断剂格列本脲预处理可阻断CCPA的作用。这些结果表明,腺苷A1受体激活减弱通过减少ROS的形成击昏。A1受体激活的这些作用似乎依赖于KATP通道的开放。
Reactive oxygen species (ROS) formation following brief periods of ischemia or hypoxia is thought to be the underlying cause of myocardial stunning. Adenosine A1receptor activation prior to ischemia/hypoxia attenuates stunning, although the mechanism for this effect remains unknown. Isolated rat ventricular myocytes loaded with the ROS-sensitive indicator dichlorofluorescin were subjected to 30 min glucose-free hypoxia followed by reoxygenation. Intracellular ROS increased 175% (from pre-hypoxic levels) during reoxygenation while cell shortening decreased 50%. In myocytes pretreated with the adenosine A1agonist 2-chloro- N6-cyclopentlyadenosine (CCPA), reoxygenation-induced ROS formation was attenuated by 40% and stunning was attenuated by 50% (compared to untreated myocytes). The mitochondrial KATPchannel opener diazoxide mimicked the effects of CCPA. Pretreatment with the mitochondrial KATPchannel blocker 5-hydroxydecanoate, or the non-selective KATPchannel blocker glibenclamide, blocked the effects of CCPA. These results suggest that adenosine A1receptor activation attenuates stunning by reducing ROS formation. These effects of A1receptor activation appear to be dependent on the opening of KATPchannels.
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