Effective pharmacotherapy against oxidative injury: alternative utility of an ATP-sensitive potassium channel opener. J Cardiovasc Pharmacol 2007 Oct;50(4):411-8
Date
12/01/2007Pubmed ID
18049309DOI
10.1097/FJC.0b013e31812378dfScopus ID
2-s2.0-37349022807 (requires institutional sign-in at Scopus site) 23 CitationsAbstract
Cardiomyocyte viability following ischemia-reperfusion critically depends on mitochondrial function. In this regard, potassium channel openers (KCOs) targeting mitochondria have emerged as powerful cardioprotective agents when applied at the onset of ischemia. However, it is controversial whether openers are still protective when applied at the onset of reoxygenation. Here, H9c2 cardiomyocytes and mitochondria isolated from the rat heart ventricle were subjected to ischemia-reoxygenation or oxidative stress in the absence or presence of 100 microM diazoxide, a potassium channel opener. Ischemia-reoxygenation or oxidative stress significantly reduced cell viability, induced structural damage in association with increased mitochondrial protein release, and impaired oxidative phosphorylation. However, treatment with diazoxide before anoxia or at the onset of reoxygenation, as well as during oxidative stress, prevented cell death and mitochondrial dysfunction and preserved cellular and mitochondrial structural integrity. These protective effects were blocked by 5-hydroxydecanoate. Thus, treatment with potassium channel openers even at the time of reoxygenation may provide a significant protection of the myocardium. The protective mechanism is at least in part endogenous to the mitochondria because protection was also observed in isolated mitochondria.
Author List
Ozcan C, Terzic A, Bienengraeber MMESH terms used to index this publication - Major topics in bold
Adenosine TriphosphateAnimals
Anti-Arrhythmia Agents
Cell Hypoxia
Cell Line
Cell Respiration
Cell Survival
Creatine Kinase
Cytochromes c
Decanoic Acids
Diazoxide
Hydrogen Peroxide
Hydroxy Acids
KATP Channels
L-Lactate Dehydrogenase
Male
Microscopy, Electron, Transmission
Mitochondria, Heart
Myocytes, Cardiac
Oxidative Phosphorylation
Oxidative Stress
Rats
