Protective Effect of FR168888, a New Na^+/H^+ Exchange Inhibitor, on Ischemia and Reperfusion-Induced Arrhythmia and Myocardial Infarction in Rats : In Comparison With Other Cardioprotective Compounds
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概要
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We have studied the effects of FR168888 (5-hydroxymethyl-3-(pyrrol-1-yl)benzoylguanidine methanesulfonate), a new Na+/H+ exchange inhibitor, on ischemia and reperfusion-induced arrhythmia and myocardial infarction in anesthetized rats and compared them with those of other cardioprotective compounds. FR168888 had a potent inhibitory effect on Na+/H+ exchange of rat lymphocytes acidified with Na+-propionate with a Ki value of 6.4 nM. Pretreatment with FR168888 (0.032 - 0.32 mg/kg, i.v.) reduced or completely abolished the ventricular fibrillation (VF) induced by reperfusion after 5 min of regional ischemia, while lidocaine, a class I antiarrhythmic agent, showed less effect against VF as compared with FR168888. The size of myocardial infarction induced by 60-min ischemia and 60-min reperfusion was attenuated by FR168888 dose-dependently (1.0 - 10 mg/kg, i.v.), and ventricular tachycardia and VF were significantly reduced during the ischemic period. In contrast, propranolol and diltiazem did not show such protective effects on myocardial infarct size. In addition, FR168888 did not change hemodynamic parameters in rats. These results indicate that FR168888 has a strong inhibitory effect on Na+/H+ exchange and that treatment with FR168888 can protect the heart from arrhythmia and myocardial cell death in ischemic and reperfused situations.
- 社団法人 日本薬理学会の論文
- 1999-08-01
著者
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MAEDA Kazuhiro
Department of Biotechnology, Tokyo University of Agriculture and Technology
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Maeda K
Department Of Gastroenterology And Medicine Faculty Of Medicine Fukuoka University
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Maeda Kazuhiro
Department Of Biotechnology Tokyo University Of Agriculture And Technology
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GOTO Toshio
Department of Quantum Engineering, Nagoya University
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Maeda Kazuhiro
Department Of Gastroenterology Fukuoka University Hospital
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Ozaki Toru
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Seki Jiro
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Ozaki Tohru
Department Of Pharmacology Hamamatsu University School Of Medicine
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Ohkubo Kazumi
Department Of Cardiovascular Diseases Medicinal Biology Research Laboratories Fujisawa Pharmaceutica
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OHARA Fumihiro
Department of Cardiovascular Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceuti
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SUGIMOTO Toshiko
Department of Cardiovascular Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceuti
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YAMAMOTO Nobuhiro
Department of Cardiovascular Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceuti
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Ohara Fumihiro
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Sugimoto Toshiko
Department Of Cardiovascular Diseases Medicinal Biology Research Laboratories Fujisawa Pharmaceutica
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Goto Toshio
Department Of Electronics Faculty Of Engineering Nagoya University
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後藤 俊夫
Imram Tohoku University
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Yamamoto Nobuhiro
Department Of Cardiovascular Diseases Medical Biology Research Laboratories
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Maeda Kazuhiro
Department Of Biotechnology Faculty Of Technology Tokyo University Of Agriculture And Technology
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Goto Toshio
Department Of Electronic Mechanical Engineering Nagoya University
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GOTO Toshio
Department of Agricultural Chemistry, Faculty of Agriculture, Nagoya University
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MAEDA Kazuhiro
Department of Bioscience and Bioinformatics, Kyushu Institute of Technology
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