Ivabradine inhibits the production of proinflammatory cytokines and inducible nitric oxide synthase in acute coxsackievirus B3-induced myocarditis.

Abstract

The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models. The beneficial action of the β-blocker carvedilol in murine viral myocarditis can be explained partly by the resulting heart rate reduction and the inhibition of proinflammatory cytokine production. The modulation of myocardial necrosis and contractile dysfunction by proinflammatory cytokines may be partially mediated by the production of nitric oxide (NO). The selective I(f) current inhibitor ivabradine reduces the heart rate without affecting cardiac contractility and has been shown to be cardioprotective in failing hearts. However, little is known about the effects of ivabradine in viral myocarditis, and in particular, its effects on inducible NO synthase (iNOS) have not been investigated. This study was therefore designed to examine the effects of ivabradine in murine viral myocarditis. In a coxsackievirus B3 murine myocarditis model, the effects of ivabradine and carvedilol on the myocardial histopathological changes and fibrosis, NO production, iNOS protein and cytokine levels were studied. Both ivabradine and carvedilol similarlyattenuated myocardial lesions and fibrosis, inhibited NO synthesis by iNOS, and decreased the production of TNF-α and IL-6. These results show that ivabradine has a therapeutic benefit in murine CVB3-induced myocarditis. The beneficial effects of ivabradine in viral myocarditis are partially mediated by the inhibition of both the production of proinflammatory cytokines and the synthesis of NO by iNOS.

• Authors: Yue-Chun Li, Qin Luo, Li-Sha Ge, Yi-He Chen, Na-Dan Zhou, Teng Zhang, Xue-Qiang Guan, Jia-Feng Lin
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 431 Issue 3 Pg. 450-5 (Feb 15 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 23333383 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Adrenergic alpha-1 Receptor Antagonists
• Benzazepines
• Carbazoles
• Cytokines
• Propanolamines
• Carvedilol
• Nitric Oxide
• Ivabradine
• Nitric Oxide Synthase Type II

Topics

• Adrenergic alpha-1 Receptor Antagonists (therapeutic use)
• Animals
• Benzazepines (therapeutic use)
• Carbazoles (therapeutic use)
• Carvedilol
• Coxsackievirus Infections (complications, drug therapy)
• Cytokines (antagonists & inhibitors, genetics)
• Gene Expression (drug effects)
• Ivabradine
• Male
• Mice
• Mice, Inbred BALB C
• Myocarditis (drug therapy, virology)
• Nitric Oxide (antagonists & inhibitors)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Propanolamines (therapeutic use)