Cardioprotective effects of 9-hydroxyellipticine on ischemia and reperfusion in isolated rat heart.
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 microM 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.
Saeki
Kazuhiko
K
Discovery Research Laboratory, Tanabe Seiyaku Co, Toda-shi, Saitama, Japan. kazu@tanabe.co.jp
Obi
Ichiro
I
Ogiku
Noriko
N
Shigekawa
Munekazu
M
Imagawa
Toshiaki
T
Matsumoto
Takeshi
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001667:Binding, Competitive; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D006224:Cricetinae; D004611:Ellipticines / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009543:Nifedipine / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D004611:Ellipticines; D019837:Ryanodine Receptor Calcium Release Channel; C008009:9-hydroxyellipticine; D009543:Nifedipine; D002118:Calcium