Role of intracellular Na+ kinetics in preconditioned rat heart
Role of intracellular Na+ kinetics in preconditioned rat heart
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DOI：
10.1161/hh1101.092139
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发表时间：
2001-06-08
影响因子：
20.1
通讯作者：
Kusuoka, H
中科院分区：
文献类型：
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作者：
Imahashi, K;Nishimura, T;Kusuoka, H
为了阐明细胞内 Na+ 动力学在缺血预处理 (IPC) 机制中的作用，我们使用 Na-23 磁共振波谱法测量了离体大鼠心脏的细胞内 Na+ 浓度 ([Na+](i))。与非 IPC 对照相比，IPC 显着延迟了初始 [Na+](i) 增加 (d[Na+](i)/dt)，导致缺血 27 分钟期间 Na+ 积累减弱 (Delta [Na+](i))，并具有更好的功能恢复。 IPC 中的 [Na+](i)（但不在对照中）在 6 分钟再灌注期间恢复至缺血前水平。 Na+-H+交换抑制剂进一步抑制对照心脏和IPC心脏中的d[Na+](i)/dt，同时改善功能恢复，表明对LPC机制几乎没有贡献。线粒体 ATP 敏感 K+ (mito K-ATP) 通道激活剂二氮嗪 (30 mu mol/L) 完全模拟了 IPC 中的 [Na+](i) 动力学和功能恢复，且对 IPC 没有任何附加作用。 Mito K-ATP通道阻断剂5-羟基癸酸(100 μmol/L)失去了保护作用以及二氮嗪诱导的d[Na+](i)/dt和[Na+](i)恢复的减弱，而5-羟基癸酸也失去了IPC诱导的保护作用，但不完全消除d[Na+](i)/dt和[Na+](i)恢复的改变。 Na+/K+-ATP酶抑制剂哇巴因（200 μmol/L）不会改变非IPC心脏中的d[Na+](i)/dt，但它消除了IPC或二氮嗪诱导的d[Na+](i)/dt降低和[Na+](i)恢复，而IPC随后哇巴因治疗显示出部分功能恢复，且Delta [Na+](i)比其他哇巴因更小组。总之，通过螨 K-ATP 通道激活介导的 Na+/K+-ATP 酶保留 Na+ 流出来改变 Na+ 动力学主要有助于 LPC 心脏的功能保护。与 Na+ 动力学相关的螨 K-ATP 通道独立途径（包括减少 Na+ 内流）的贡献在 IPC 的功能保护中受到限制。
To elucidate the role of intracellular Na+ kinetics in the mechanism for ischemic preconditioning (IPC), we measured intracellular Na+ concentration ([Na+](i)) using Na-23-magnetic resonance spectroscopy in isolated rat hearts. IPC significantly delayed the initial [Na+](i) increase (d[Na+](i)/dt) compared with non-IPC control, resulting in attenuation of Na+ accumulation (Delta [Na+](i)) during 27 minutes of ischemia with better functional recovery. [Na+](i) in IPC, but not in control, recovered to preischemic level during a 6-minute reperfusion. The Na+-H+ exchange inhibitor further suppressed d[Na+](i)/dt in both control and IPC hearts with concomitant improvement of functional recovery, suggesting little contribution to the mechanism of LPC. The mitochondrial ATP-sensitive K+ (mito K-ATP) channel activator diazoxide (30 mu mol/L) completely mimicked both [Na+](i) kinetics and functional recovery in IPC without any additive effects to IPC. The mito K-ATP channel blocker 5-hydroxydecanoic acid (100 mu mol/L) lost protective effect as well as the attenuation of d[Na+](i)/dt and [Na+](i) recovery induced by diazoxide, However, 5-hydroxydecanoic acid also lost IPC-induced protection, but incompletely abolished the alteration of d[Na+](i)/dt and the [Na+](i) recovery. The Na+/K+-ATPase inhibitor ouabain (200 mu mol/L) did not change d[Na+](i)/dt in non-IPC hearts, but it abolished the IPC- or diazoxide-induced reduction of d[Na+](i)/dt and the [Na+](i) recovery, whereas IPC followed by ouabain treatment showed partial functional recovery with smaller Delta [Na+](i) than other ouabain groups. In conclusion, alteration of Na+ kinetics by preserving Na+ efflux via Na+/K+-ATPase mediated by mite K-ATP channel activation mainly contributes to functional protection in LPC hearts. The contribution of mite K-ATP channel-independent pathway relating to Na+ kinetics including reduced Na+ influx is limited in functional protection of IPC.