© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Remote preconditioning protects the heart by activating myocardial PKC
-isoform
Institute for Experimental and Clinical Pharmacology and Toxicology, Medical University of Lübeck, Lübeck, Germany
* Corresponding author. Present address: Medizinische Klinik II, Universitätsklinikum Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. Tel.: +49-451-500-2421; fax: +49-451-500-6616 wolfrum{at}medinf.mu-luebeck.de
Objective: Myocardial protection can be achieved by brief ischemia-reperfusion of remote organs, a phenomenon described as remote preconditioning (RPC). Since the intracellular mechanisms of RPC are not known, we tested the hypothesis that RPC might activate myocardial PKC
, an essential mediator of classical ischemic preconditioning. Furthermore, we tried to delineate the mechanisms by which RPC is transduced to the heart with respect to the possible contribution of kinins and neuronal reflexes. Methods: Anesthetized rats were randomised to undergo either 30 min of waiting (controls) or RPC (brief mesenteric artery occlusion followed by reperfusion) in the absence or presence of chelerythrine (5 mg kg–1), a specific PKC inhibitor. Myocardial infarct size was measured by TTC staining after 30 min of coronary artery occlusion followed by 150 min of reperfusion. In separate sets of experiments RPC was performed with or without pretreatment with HOE140, a selective B2-antagonist or hexamethonium was used to explore the influence of ganglion blockade on RPC. Translocation of PKC from cytosol to the particulate fraction was measured by quantitative immunoblotting. Results: RPC significantly reduced infarct size which was completely blocked by the PKC inhibitor. RPC shifted the ratio between cytosolic and particulate PKC, an indicator for PKC-activation, from 0.95±0.06 in controls to 0.41±0.09 (P<0.05), and this effect was abolished by HOE140. Activation of PKC could not be achieved after pretreatment with HEX (0.69±0.06 in HEX vs. 0.78±0.06 in HEX+RPC). Conclusions: RPC activates myocardial PKC through a neuronal and bradykinin-dependent pathway. We assume that activation of PKC is an important step in cardioprotection induced by remote preconditioning.
KEYWORDS Endothelial receptors; Infarction; Neurotransmitters; Preconditioning; Protein kinases
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