Carvedilol treatment ameliorates acute coxsackievirus B3-induced myocarditis associated with oxidative stress reduction

• Published in: European journal of pharmacology Vol. 640; no. 1; pp. 112 - 116
• Main Authors: Yue-Chun, Li, Li-Sha, Ge, Peng-Lin, Yang, Ji-Fei, Tang, Jia-Feng, Lin, Peng, Chen, Xue-qiang, Guan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.08.2010; Elsevier
• Subjects: 4-Hydroxy-2-nonenal; Adrenergic Antagonists - pharmacology; Adrenergic Antagonists - therapeutic use; Aldehydes - metabolism; Animals; Biological and medical sciences; Body Weight - drug effects; Carbazoles - pharmacology; Carbazoles - therapeutic use; Cardiology. Vascular system; Carvedilol; Coxsackievirus B3; Electrocardiography; Enterovirus - physiology; Glutathione Peroxidase - metabolism; Heart; Heart - drug effects; Heart - physiopathology; Hemodynamics - drug effects; Male; Malondialdehyde - metabolism; Medical sciences; Metoprolol - pharmacology; Mice; Mice, Inbred BALB C; Myocarditis - drug therapy; Myocarditis - metabolism; Myocarditis - pathology; Myocarditis - virology; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Myocardium - pathology; Organ Size - drug effects; Oxidative Stress - drug effects; Pharmacology. Drug treatments; Propanolamines - pharmacology; Propanolamines - therapeutic use; Superoxide Dismutase - metabolism; Survival Rate; Time Factors; Viral Load - drug effects; Viral myocarditis; 4-Hydroxy-2-nonenal; Carvedilol; Viral myocarditis; Oxidative stress; Vasodilator agent; Picornaviridae; Acute; α1-Adrenergic receptor; Cardiovascular disease; β2-Adrenergic receptor; Enterovirus; Myocardial disease; Virus; Myocarditis; Alpha blocking agent; β1-Adrenergic receptor; Treatment; Heart disease; Coxsackievirus B3; Antihypertensive agent; Antagonist; Beta blocking agent
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.04.037

Oxidative stress has been implicated in the pathogenesis of acute myocarditis. The imbalance between the occurrence of reactive oxygen species and the cellular antioxidant defense mechanism plays a key role in myocardial injury of viral myocarditis. Carvedilol, a nonselective β-adrenoceptor antagonist with additional α 1-adrenergic blocking and antioxidant properties, has been shown to be cardioprotective in experimental myocarditis. However, the expression of 4-hydroxy-2-nonenal (4-HNE), the most reliable marker of lipid peroxidation, has not been studied, and the antioxidative effects of carvedilol have not been investigated in the setting of acute viral myocarditis. This study was therefore designed to determine whether levels of lipid peroxides are elevated in the myocardium and whether carvedilol reduces the lipid peroxidation level and increases antioxidant enzyme activities. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol and metoprolol on 14-day survival rate, myocardial histopathological changes, cardiac function, the expression of 4-HNE, virus titers, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidases (GSH-Px) activities were studied. Lipid peroxidations including 4-HNE and MDA, were elevated in murine coxsackievirus-induced acute viral myocarditis. Carvedilol, but not metoprolol, improved survival, reduced lipid peroxidations including 4-HNE and MDA, and increased antioxidant enzyme activities including SOD and GSH-Px with amelioration of acute viral myocarditis. These results show that carvedilol but not metoprolol exerts some of its beneficial effects by inhibiting peroxidants.