caa a22 4500 475833775 CHVBK 20180406123848.0 cr unu---uuuuu 170329e20001001xx s 000 0 eng 10.1023/A:1007837022300 doi (NATIONALLICENCE)springer-10.1023/A:1007837022300 Infarct Size Limitation by Bradykinin Receptor Activation Is Mediated by the Mitochondrial But Not by the Sarcolemmal KATP Channel [Elektronische Daten] [Hiroyuki Kita, Tetsuji Miura, Takayuki Miki, Satoshi Genda, Masaya Tanno, Takayuki Fukuma, Kazuaki Shimamoto] 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 (KATP) channel in the mitochondria (mito-KATP channel) or KATP channel in the sarcolemma (sarc-KATP 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 μmol/L), a selective mito-KATP channel blocker (% IS/AR = 44.2 ± 6.4). In contrast, a high dose of HMR1098 (20 μmol/L), which is a newly developed sarc-KATP channel selective blocker with IC50 of 0.6 μmol/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-KATP channel but not the sarc-KATP channel is involved in infarct size limitation by a mechanism triggered by bradykinin B2 receptor activation. Kluwer Academic Publishers, 2000 bradykinin nationallicence infarct size nationallicence ATP-sensitive potassium channel nationallicence mitochondria nationallicence Kita Hiroyuki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Miura Tetsuji Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Miki Takayuki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Genda Satoshi Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Tanno Masaya Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Fukuma Takayuki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Shimamoto Kazuaki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/5(2000-10-01), 497-502 0920-3206 14:5<497 2000 14 10557 https://doi.org/10.1023/A:1007837022300 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1007837022300 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kita Hiroyuki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Miura Tetsuji Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Miki Takayuki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Genda Satoshi Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Tanno Masaya Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Fukuma Takayuki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 700 1- Shimamoto Kazuaki Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Kluwer Academic Publishers 14/5(2000-10-01), 497-502 0920-3206 14:5<497 2000 14 10557 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer