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KMID : 0857020050200010147
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Kosin Medical Journal
2005 Volume.20 No. 1 p.147 ~ p.156
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Cardioprotective Effect of cGMP/PKG-dependent Signaling Mechanism
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Park Kyeong-Lok
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Abstract
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Backgrounds: The present investigation tested the hypothesis that cGMP-dependent protein kinase (PKG) activates ATP sensitive K+ (KATP) channels and thus could be associated with the cardioprotective response of ischemic preconditioning.
Methods: PKG-induced KATP channel activation and its cardioprotective effects were studied in rabbit ventricular myocytes using path-clamp techniques and in hear slice model for simulated ischemia and preconditioning.
Results: No donors and PKG activators facilitated KATP channel activity in a concentration dependent manner, and their effects were suppresed by PKG inhibitors. Exogenous PKG increased KATP channel activity by a phosphorylation-dependent machanism. Heart slices preconditioned with a single 5-min anoxia followed by 15-min reoxygenation were protected against subsequent 30-min anoxia and 60-min reoxygenation. The beneficial effects of anoxia were almost completely prevented by blibenclamide and PKG inhibitor. Pretreatment with NO donor or PKG activator mimicked anoxic preconditioning. In heart slices pretreated with NO donor or PKG activator, the cardioprotection was blocked by the concomitant presence of glibenclamide or PKG inhibitor.
Conclusion: Taken together with the above results showing that the KATP channel acts downstream of the PKG-pathway in the mediating the protective effect, these data indicate that this mechanism, at least in part, contributes to a signaling pathway that induces ischemic preconditioning.
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KEYWORD
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cGMP-dependent protein kinase(PKG), ATP-sensitive K+(KATP) channels, ischemic preconditioning, rabbit ventricular myocyte
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