Nitric Oxide-cgmp-protein Kinase G Signaling Pathway Induces Anoxic Preconditioning Through Activation of Atp-sensitive K+ Channels in Rat Hearts.
From: Mitochondrial Signaling Laboratory, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Biohealth Products Research Center, Inje University, Busan, Korea.
American journal of physiology. Heart and circulatory physiology
- Publish Date: May 2006
- ISSN: 0363-6135
- Volume: 290
- Issue: 5
- Pages: H1808-17
- Medium: Print
- Language: English
- Citation (JAMA): Cuong Dang Van, Kim Nari, Youm Jae Boum, et al. Nitric Oxide-cgmp-protein Kinase G Signaling Pathway Induces Anoxic Preconditioning Through Activation of Atp-sensitive K+ Channels in Rat Hearts.. Am. J. Physiol. Heart Circ. Physiol. May 2006;290:H1808-17
Abstract
Nitric oxide (NO) plays an important role in anoxic preconditioning to protect the heart against ischemia-reperfusion injuries. The present work was performed to study better the NO-cGMP-protein kinase G (PKG) signaling pathway in the activation of both sarcolemmal and mitochondrial ATP-sensitive K+ (KATP) channels during anoxic preconditioning (APC) and final influence on reducing anoxia-reperfusion (A/R)-induced cardiac damage in rat hearts. The upstream regulating elements controlling NO-cGMP-PKG signal-induced KATP channel opening that leads to cardioprotection were investigated. The involvement of both inducible and endothelial NO synthases (iNOS and eNOS) in the progression of this signaling pathway was followed. Final cellular outcomes of ischemia-induced injury after different preconditioning in the form of lactate dehydrogenase release, DNA strand breaks, and malondialdehyde formation as indexes of cell injury and lipid peroxidation, respectively, were investigated. The lactate dehydrogenase and malondialdehyde values decreased in the groups that underwent preconditioning periods with specific mitochondrial KATP channels opener diazoxide (100 microM), nonspecific mitochondrial KATP channels opener pinacidil (50 microM), S-nitroso-N-acetylpenicillamine (SNAP, 300 microM), or beta-phenyl-1,N2-etheno-8-bromoguanosine-3’,5’-cyclicmonophosphorothioate, Sp-isomer (10 microM) before the A/R period. Preconditioning with SNAP significantly reduced the DNA damage. The effect was blocked by glibenclamide (50 microM), 5-hydroxydecanoate (100 microM), NG-nitro-L-arginine methyl ester (200 microM), and beta-phenyl-1,N2-etheno-8-bromoguanosine-3’,5’-cyclic monophosphorothioate, Rp-isomer (1 microM). The results suggest iNOS, rather than eNOS, as the major contributing NO synthase during APC treatment. Moreover, the PKG shows priority over NO as the upstream regulator of NO-cGMP-PKG signal-induced KATP channel opening that leads to cardioprotection during APC treatment.
Mesh Headings (Keywords): Animals, Cells, Cultured, Cyclic GMP, Cyclic GMP-Dependent Protein Kinases, Ischemic Preconditioning, Male, Myocytes, Cardiac, Nitric Oxide, Oxidative Stress, Potassium Channels, Rats, Rats, Sprague-Dawley, Signal Transduction
Check for Full Text / PubMed Unique Identifier (PMID): 16339835
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