Nitric Oxide-cGMP-Protein Kinase G Pathway Contributes to Cardioprotective Effects of ATP-Sensitive K+ Channels in Rat Hearts
The Korean Journal of Physiology and Pharmacology
;
: 95-100, 2004.
Artigo
em Inglês
| WPRIM
| ID: wpr-728496
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosfotransferases
/
Potássio
/
Dano ao DNA
/
DNA
/
Reperfusão
/
Glibureto
/
Precondicionamento Isquêmico
/
Células Musculares
/
Diazóxido
/
Eletroforese
Tipo de estudo:
Estudo diagnóstico
Limite:
Animais
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2004
Tipo de documento:
Artigo
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