title: Landiolol has cardioprotective effects against reperfusion injury in the rat heart via the PKCepsilon signaling pathway.
abstract: 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.
authors.affiliation: Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan. ysk@msic.med.osaka-cu.ac.jp
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Minamiyama
authors.forename: Tohihiko
authors.initials: T
authors.lastname: Shibata
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Hirai
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Shigefumi
authors.initials: S
authors.lastname: Suehiro
mesh_terms: 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
chemical_list: 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