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	Yosuke Takahashi, Shigekazu Takemura, Yukiko Minamiyama, Tohihiko Shibata, Hidekazu Hirai, Yasuyuki Sasaki, Masanori Sakaguchi, Shigefumi Suehiro
Journal	Free radical research (Free Radic Res) Vol. 41 Issue 7 Pg. 757-69 (Jul 2007) ISSN: 1071-5762 [Print] England
PMID	17577736 (Publication Type: Journal Article)
Chemical References	Adrenergic beta-Antagonists Alkaloids Benzophenanthridines Cardiotonic Agents Morpholines landiolol Urea chelerythrine Protein Kinase C-epsilon Glyburide
Topics	Adrenergic beta-Antagonists (pharmacology) Alkaloids (pharmacology) Animals Benzophenanthridines (pharmacology) Cardiotonic Agents (pharmacology) Glyburide (pharmacology) Heart (drug effects, physiology) Ischemic Preconditioning Male Morpholines (pharmacology) Myocardial Ischemia (prevention & control) Phosphorylation Protein Kinase C-epsilon (drug effects, metabolism) Rats Rats, Wistar Reperfusion Injury (prevention & control) Signal Transduction (drug effects) Urea (analogs & derivatives, pharmacology)

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