Korean J Physiol Pharmacol 2004; 8(2): 95-100
Published online April 30, 2004
Copyright © Korean J Physiol Pharmacol.
Dang Van Cuong*, Nari Kim*, Hee Cheol Cho, Euiyong Kim, and Jin Han
Department of Physiology & Biophysics, Molecular Cell Physiology Research Group, Biohealth Products Research Center, College of Medicine, Inje University, Busan 614－735, Korea
Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium (KATP) channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that KATP channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide (100μM), SNAP (300μM) and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) (100μM) followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide (50μM), 5-hydroxydecanoate (5-HD) (100μM) and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) (100μM). These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of KATP channels in rat ventricular myocytes.
Keywords: Nitric oxide, ATP-sensitive K, channel, Oxidative damage, Ischemic preconditioning
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