Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes
Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes
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DOI：
10.1124/jpet.105.092023
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发表时间：
2006-02-01
影响因子：
3.5
通讯作者：
Moore, PK
中科院分区：
文献类型：
--
作者：
Bian, JS;Yong, QC;Moore, PK
内源性H2S主要由心脏内的半胱硫氨酸γ -裂解酶合成。本研究探讨H2S在缺血预处理诱导的心脏保护中的作用。我们研究了内源性H2S和外源性NaHS （H2S供体）对低流量缺血大鼠离体心脏心律的影响，以及暴露于模拟缺血溶液的离体心肌细胞的细胞活力和功能。NaHS （SP）或缺血（IP）预处理3个周期（每个周期3分钟，间隔5分钟的恢复时间）可显著降低离体心脏缺血/再灌注引起的心律失常的持续时间和严重程度，同时增加心肌细胞活力和缺血/再灌注后电诱导钙瞬态的幅度。IP和SP均能显著减轻缺血时H2S生成的减少。此外，内源性H2S产生的减少显著减弱了IP对离体心脏和离体心肌细胞的保护作用。用chelerythrine或双吲哚聚马来酰亚胺I阻断蛋白激酶C，以及用glibenclamide（一种非选择性K- atp阻断剂）和HMR-1098（1-[[5-[2-（5-氯-o-氨基异胺）乙基]-2-甲氧基苯基]磺酰]-3-甲基硫脲）（一种肌层K- atp通道阻断剂）阻断atp敏感K+ (K- atp)通道)逆转SP或IP诱导的心脏保护作用。然而，用5-羟基乙酸阻断线粒体K-ATP通道对SP的心脏保护没有影响，这表明，与IP所涉及的机制不同，线粒体K-ATP通道很可能在SP的心脏保护中不起主要作用。我们的研究结果表明，内源性H2S有助于IP诱导的心脏保护，其作用可能涉及蛋白激酶C和肌层K-ATP通道。
Endogenous H2S is synthesized mainly by cystathionine gamma-lyase in the heart. The present study investigated the role of H2S in cardioprotection induced by ischemic preconditioning. We have examined the effect of endogenous H2S and exogenous application of NaHS (H2S donor) on cardiac rhythm in the isolated rat heart subjected to low-flow ischemia insults as well as cell viability and function in isolated myocytes exposed to simulated ischemia solution. Preconditioning with NaHS (SP) or ischemia (IP) for three cycles (3 min each cycle separated by 5 min of recovery) significantly decreased the duration and severity of ischemia/reperfusion-induced arrhythmias in the isolated heart while increasing cell viability and the amplitude of electrically induced calcium transients after ischemia/reperfusion in cardiac myocytes. Both IP and SP also significantly attenuated the decreased H2S production during ischemia. Moreover, decreasing endogenous H2S production significantly attenuated the protective effect of IP in both the isolated heart and isolated cardiac myocytes. Blockade of protein kinase C with chelerythrine or bisindolylmaleimide I as well as ATP-sensitive K+ (K-ATP) channel with glibenclamide (a nonselective K-ATP blocker) and HMR-1098 (1-[[5-[2-(5-Chloro-o-anisamido) ethyl]-2-methoxyphenyl] sulfonyl]-3-methylthiourea) (a sarcolemmal K-ATP channel blocker) reversed the cardioprotection induced by SP or IP. However, blockade of mitochondrial K-ATP channels with 5- hydroxydecanoic acid had no effect on the cardioprotection of SP, suggesting that, unlike the mechanism involved in IP, mitochondrial K-ATP channels most probably do not play a major role in the cardioprotection of SP. Our findings suggest that endogenous H2S contributes to cardioprotection induced by IP, which effect may involve protein kinase C and sarcolemmal K-ATP channels.