Cardioprotective Effects of 9-Hydroxyellipticine on Ischemia and Reperfusion in Isolated Rat Heart
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概要
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We determined the effect of 9-hydroxyellipticine (9HE) on ryanodine receptor (RyR) and cardiac function after global ischemia in isolated rat hearts. The binding of [3H]-ryanodine in rabbit cardiac sarcoplasmic reticulum was displaced by 9HE in a biphasic manner corresponding to the two sites model with IC50 values of 6.1 μM and 55 mM. The increase of the intracellular Ca2+ concentration induced by caffeine in CHO cells expressing cardiac-type RyR was suppressed by 9HE in a concentration-dependent manner. Pretreatment of the heart with 9HE decreased the total duration of reperfusion-induced ventricular fibrillation (VF) and delayed the onset of VF. There was also a significant recovery of contractile force of ischemic hearts following 9HE. Unlike nifedipine, an L-type Ca2+-channel blocker, 9HE did not suppress the contraction of rat papillary muscles. Thus, 9HE exerts the cardioprotective effects against ischemia/reperfusion injury without changing hemodynamic indices.
- 2002-05-01
著者
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IMAGAWA Toshiaki
Division of Chemistry, Graduate School of Science, Hokkaido University
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SHIGEKAWA Munekazu
Department of Melecular Physiology, National Cardiovascular Center Research Institute
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Saeki Kazuhiko
田辺製薬
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Obi Ichiro
Discovery Research Laboratory Tanabe Seiyaku Co.
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Saeki Kazuhiko
Discovery Research Laboratory Tanabe Seiyaku Co.
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OGIKU Noriko
Discovery Research Laboratory, Tanabe Seiyaku Co.
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MATSUMOTO Takeshi
Discovery Research Laboratory, Tanabe Seiyaku Co.
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Shigekawa Munekazu
Department Of Molecular Physiology National Cardiovascular Center Research Institute
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Ogiku Noriko
Discovery Research Laboratory Tanabe Seiyaku Co.
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Imagawa Toshiaki
Division Of Chemistry Biochemistry Graduate School Of Science Hokkaido University
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Shigekawa Munekazu
Department Of Food And Nutrition Faculty Of Human Life Sciences Senri Kinran University
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Matsumoto Takeshi
Discovery Research Laboratory Tanabe Seiyaku Co.
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