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

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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.