Landiolol has cardioprotective effects against reperfusion injury in the rat heart via the PKCepsilon signaling pathway.
Landiolol, a highly cardioselective beta1-blocker, has cardioprotective effects against ischemia-reperfusion injury, although the precise mechanism is still unclear. The aim of this study was to clarify the cardioprotective mechanism of landiolol. Experiments were performed on Langendorff-perfused rat hearts undergoing 20 min stabilization, and 45 min of ischemia followed by 60 min of reperfusion. Various drugs with or without landiolol (100 microM) were administered before ischemia for 20 min. Preischemic administration of landiolol reduced cardiac cellular damage and improved the recovery of cardiac function by about 40%. The alpha1 blocker prazosin, the protein kinase C (PKC) inhibitor chelerythrine or the K(ATP) channel blocker glibenclamide, but not the selective mitochondrial K(ATP) channel blocker 5-hydroxydecanoate abrogated the cardioprotective effect induced by landiolol. Following landiolol pretreatment the activation of PKCepsilon and heat shock protein 27 were significantly higher than that in control. These data indicate that preischemic application of landiolol induces cardioprotective effects through PKCepsilon-mediated pathway, similar to that afforded by ischemic preconditioning.
Takahashi
Yosuke
Y
Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan. ysk@msic.med.osaka-cu.ac.jp
Takemura
Shigekazu
S
Minamiyama
Yukiko
Y
Shibata
Tohihiko
T
Hirai
Hidekazu
H
Sasaki
Yasuyuki
Y
Sakaguchi
Masanori
M
Suehiro
Shigefumi
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D019194:Ischemic Preconditioning; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000517:prevention & control; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000470:Alkaloids; D053119:Benzophenanthridines; D002316:Cardiotonic Agents; D009025:Morpholines; C077049:landiolol; D014508:Urea; C016299:chelerythrine; D051744:Protein Kinase C-epsilon; D005905:Glyburide