Experimental and clinical evaluation of cardioprotective effects by adenosine and nitric oxide

在发达国家，心肌梗死后心律失常和随后的心力衰竭已成为心源性死亡的主要原因。本研究旨在阐明急性心肌梗死后心血管损伤的机制，并探索缺血应激后心肌保护的新方法。本研究采用大鼠和犬缺血模型，研究了短暂缺血后血管舒张的作用和缺血预适应现象，发现NO和K通道开放剂的产生与缺血预适应相似。腺苷对缺血后心肌也有保护作用，提示腺苷和NO通路在缺血预适应现象中起重要作用。然后我们发现，常用的抗高血压药物卡维地洛和卡维地洛通过产生NO和腺苷来扩张血管，从而保护缺血性损伤。腺苷和NO的细胞内信号传导也被检测，并揭示了PKC和PKA在这种保护作用中的参与，因为我们得出结论，NO和腺苷是保护这些缺血性损伤的关键分子，我们开始了腺苷信号增强剂在心力衰竭的临床应用。我们将继续在临床和实验上研究腺苷在各种情况下对心血管功能的影响。

In the developed country, arrhythmia and subsequent heart failure after myocardial infarction have been major cause of cardiac death. This study was designed to elucidate the mechanism of cardiovascular injury after acute myocardial infarction and develop the novel method to protect myocardial damage after ischemic stress. We especially examined the ischemia preconditioning phenomenon and role of vasodilatation after brief ischemia using rat or canine ischemia model.In this study, we showed that production of NO and K channel opener mimicked ischemic preconditioning. Adenosine was also revealed to have cardioprotective effect after ischemia suggesting adenosine and NO pathway plays an important role of ischemia preconditioning phenomenon. Then we showed that common anti-hypertensive medicine carvedirol and amlodipine protect ischemic injury by vascular dilation via production of NO and adenosine. Intracellular signaling of adenosine and NO was also examined and revealed the involvement of PKC and PKA in this protective effect.Since we concluded that NO and adenosine are key molecules for protecting these ischemic damages, we started the clinical use of adenosine signal enhancer for heart failure. We will continue to examine the effect of adenosine for cardiovascular function in various conditions clinically and experimentally.