Adenosine and Cardioprotection in the Diseased Heart
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概要
- 論文の詳細を見る
Biological and mechanical stressors such as ischemia, hypoxia, cellular ATP depletion, Ca^<2+> overload, free radicals, pressure and volume overload, catecholamines, cytokines, and renin-angiotensin may independently cause reversible and/or irreversible cardiac dysfunction. As a defense against these forms of stress, several endogenous self-protective mechanisms are exerted to avoid cellular injury. Adenosine, a degradative substance of ATP, may act as an endogenous cardioprotective substance in pathophysiological conditions of the heart, such as myocardial ischemia and chronic heart failure. For example, when brief periods of myocardial ischemia precede sustained ischemia, infarct size is markedly limited, a phenomenon known as ischemic preconditioning. We found that ischemic preconditioning activates the enzyme responsible for adenosine release, ie, ecto-5'-nucleotidase. Furthermore, the inhibitor of ecto-5'-nucleotidase reduced the infarct size-limiting effect of ischemic preconditioning, which establishes the cause-effect relationship between activation of ecto-5'-nucleotidase and the infarct size-limiting effect. We also found that protein kinase C is responsible for the activation of ecto-5'-nucleotidase. Protein kinase C phosphorylated the serine and threonine residues of ecto-5'-nucleotidase. Therefore, we suggest that adenosine produced via ecto-5'-nucleotidase gives cardioprotection against ischemia and reperfusion injury. Also, we found that plasma adenosine levels are increased in patients with chronic heart failure. Ecto-5'-nucleotidase activity increased in the blood and the myocardium in patients with chronic heart failure, which may explain the increases in adenosine levels in the plasma and the myocardium. In addition, we found that further elevation of plasma adenosine levels due to either dipyridamole or dilazep reduces the severity of chronic heart failure. Thus, we suggest that endogenous adenosine is also beneficial in chronic heart failure. We propose potential mechanisms for cardioprotection attributable to adenosine in pathophysiological states in heart diseases. The establishment of adenosine therapy may be useful for the treatment of either ischemic heart diseases or chronic heart failure.
- 社団法人日本循環器学会の論文
- 1999-03-20
著者
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Node Koichi
Department Of Cardiovascular&renal Medicine Saga University Faculty Of Medicine
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Minamino Tetsuo
Department Of Cardiovascular Medicine Osaka University Graduate School Of Medicine
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Matsuura Kaoru
国立循環器病センター
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Takashima Seiji
Department Of Cardiology Osaka University Graduate School Of Medicine
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Shimazu Takashi
The First Department Of Medicine Osaka University School Of Medicine
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TAKASHIMA SEIJI
The First Department of Medicine, Osaka University School of Medicine
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Kitakaze Masafumi
The First Department Of Medicine Osaka University School Of Medicine
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Kuzuya Tsunehiko
The First Department Of Medicine Osaka University Medicial School
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Hori Masatsugu
The First Department Of Medicine Osaka University Medicial School
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Minamino Tetsuo
The First Department of Medicine, Osaka University School of Medicine
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Node Koichi
The First Department of Medicine, Osaka University School of Medicine
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Funaya Hiroharu
The First Department of Medicine, Osaka University School of Medicine
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Funaya Hiroharu
The First Department Of Medicine Osaka University School Of Medicine
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Hori Masatsugu
The First Department Of Medicine And The Department Of Medical Information Science
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Node Kouichi
Department Of Internal Medicine Aand Therapeutics Osaka University Graduate School Of Medicine
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