title: Infarct size limitation by bradykinin receptor activation is mediated by the mitochondrial but not by the sarcolemmal K(ATP) channel.
abstract: Earlier studies have shown that activation of bradykinin B2 receptor triggers protein kinase C (PKC)-mediated cardioprotective mechanism in ischemic preconditioning (PC). In the present study, we examined whether the effector in this B2-receptor triggered pathway of PC is the ATP sensitive potassium (K(ATP)) channel in the mitochondria (mito-K(ATP) channel) or K(ATP) channel in the sarcolemma (sarc-K(ATP) channel). Isolated rabbit hearts were perfused with modified Krebs-Henseleit buffer in a Langendorff mode, and regional myocardial ischemia was induced by occluding a left coronary artery for 30 min and then reperfusing for 2 hours. Infarct size was determined by triphenyltetrazolium chloride staining and expressed as a percentage of area at risk (% IS/AR). Infusion of bradykinin (500 nmol/L) for 15 min prior to ischemia significantly reduced % IS/AR from 37.4 +/- 2.9 (SE) of the untreated controls to 12.0 +/- 3.3%. This protective effect of bradykinin was completely abolished by coinfusion of 5-hydroxydecanoate (5-HD, 50 micromol/L), a selective mito-K(ATP) channel blocker (% IS/AR = 44.2 +/- 6.4). In contrast, a high dose of HMR1098 (20 micromol/L), which is a newly developed sarc-K(ATP) channel selective blocker with IC50 of 0.6 micromol/L, failed to modify the infarct size limitation by preischemic infusion of bradykinin (% IS/AR = 11.7 +/- 3.4). Neither 5-HD nor HMR1098 alone modified infarct size (% IS/AR = 37.8 +/- 3.8 and 35.1 +/- 6.2, respectively). These results suggest that opening of the mito-K(ATP) channel but not the sarc-K(ATP) channel is involved in infarct size limitation by a mechanism triggered by bradykinin B2 receptor activation.
authors: Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan.
authors: H
authors: H
authors: Kita
authors: T
authors: T
authors: Miura
authors: T
authors: T
authors: Miki
authors: S
authors: S
authors: Genda
authors: M
authors: M
authors: Tanno
authors: T
authors: T
authors: Fukuma
authors: K
authors: K
authors: Shimamoto
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D003652:Decanoic Acids / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009929:Organ Size / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects*; D011817:Rabbits; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D001549:Benzamides; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C052853:5-hydroxydecanoic acid; C410297:HMR 1098; D001920:Bradykinin