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: H Kita, T Miura, T Miki, S Genda, M Tanno, T Fukuma, K Shimamoto
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 14 Issue 5 Pg. 497-502 (Oct 2000) ISSN: 0920-3206 [Print] United States
• PMID: 11101197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Arrhythmia Agents
• Benzamides
• Decanoic Acids
• Hydroxy Acids
• Potassium Channels
• Receptor, Bradykinin B2
• Receptors, Bradykinin
• 5-hydroxydecanoic acid
• HMR 1098
• Bradykinin

Topics

• Analysis of Variance
• Animals
• Anti-Arrhythmia Agents (pharmacology)
• Benzamides (pharmacology)
• Bradykinin (antagonists & inhibitors, therapeutic use)
• Decanoic Acids (pharmacology)
• Hemodynamics (drug effects)
• Hydroxy Acids (pharmacology)
• Male
• Myocardial Infarction (prevention & control)
• Organ Size (drug effects)
• Potassium Channels (drug effects)
• Rabbits
• Receptor, Bradykinin B2
• Receptors, Bradykinin (drug effects)