Nitric Oxide-cGMP-Protein Kinase G Pathway Contributes to Cardioprotective Effects of ATP-Sensitive K+ Channels in Rat Hearts.
- Author:
Dang Van CUONG
1
;
Nari KIM
;
Hee Cheol CHO
;
Euiyong KIM
;
Jin HAN
Author Information
1. Department of Physiology & Biophysics, Molecular Cell Physiology Research Group, College of Medicine, Inje University, Busan 614-735, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Nitric oxide;
ATP-sensitive K+ channel;
Oxidative damage;
Ischemic preconditioning
- MeSH:
Animals;
Anoxia;
Diazoxide;
DNA;
DNA Damage;
Electrophoresis;
Glyburide;
Heart*;
Infarction;
Ischemia;
Ischemic Preconditioning;
KATP Channels;
Muscle Cells;
Nitric Oxide;
Phosphotransferases*;
Potassium;
Rats*;
Reperfusion
- From:The Korean Journal of Physiology and Pharmacology
2004;8(2):95-100
- CountryRepublic of Korea
- Language:English
-
Abstract:
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 (100muM), SNAP (300muM) and 8- (4-Chlorophenylthio)-guanosine-3', 5'-cyclic monophosphate (8-pCPT-cGMP) (100muM) 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 (50muM), 5-hydroxydecanoate (5-HD) (100muM) and 8- (4-Chlorophenylthio)-guanosine-3', 5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) (100muM). These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of KATP channels in rat ventricular myocytes.
