Abstract
Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Arrhythmia Agents / pharmacology*
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Arrhythmias, Cardiac / drug therapy*
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Arrhythmias, Cardiac / metabolism*
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Calcium / metabolism*
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Catecholamines / pharmacology
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Dietary Supplements
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Homeostasis / drug effects
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Isoproterenol / pharmacology
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Male
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Mice, Inbred Strains
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Myocardial Ischemia / complications
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Myocytes, Cardiac / drug effects
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Myocytes, Cardiac / metabolism
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Nitro Compounds / pharmacology*
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Oleic Acids / pharmacology*
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Phosphorylation / drug effects
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Ryanodine Receptor Calcium Release Channel / metabolism
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Tachycardia, Ventricular / etiology
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Tachycardia, Ventricular / prevention & control
Substances
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Anti-Arrhythmia Agents
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Catecholamines
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Nitro Compounds
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Oleic Acids
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Ryanodine Receptor Calcium Release Channel
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ryanodine receptor 2. mouse
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CXA-10
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Isoproterenol
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Calcium