Protective effects of carvedilol in murine model with the coxsackievirus B3-induced viral myocarditis.
Carvedilol, a nonselective beta-blocker with additional alpha1-adrenergic blocking and antioxidant properties, has been shown to be cardioprotective in experimental myocarditis. However, the antioxidative effects of carvedilol have not been investigated in the setting of acute viral myocarditis. Therefore, this study investigated whether carvedilol protects against viral myocarditis primarily by its antioxidant and/or antiinflammatory properties. In a coxsackievirus B3 murine myocarditis model (Balb/c), effects of carvedilol and metoprolol on myocardial histopathological changes, cytokine levels, virus titers, malondialdehyde (MDA), and superoxide dismutase (SOD) contents were studied. Carvedilol markedly attenuated myocardial lesions and increased interferon-gamma and interleukin-12 production (cytokines) on day 7 with concomitant reduction of myocardial virus replication. In addition, only carvedilol decreased the content of MDA and increased the content of SOD on day 14. Metoprolol as well as bunazosin (a higly selective alpha1-adrenergic blocking agent) had no significant effects in this model. The results indicate that the superior protection of carvedilol in this model is probably the result of its antioxidative effects and the upregulation of antiinflammatory cytokines.
Yue-Chun
Li
L
Department of Cardiology, Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, China. heifeng1980@sina.com.cn
Li-Sha
Ge
G
Jiang-Hua
Ren
R
Peng-Lin
Yang
Y
Jia-Feng
Lin
L
Ji-Fei
Tang
T
Peng
Chen
C
Zhan-Qiu
Yang
Y
D000208:Acute Disease; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D000077261:Carvedilol; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000472:pathogenicity; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D011412:Propanolamines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002227:Carbazoles; D002316:Cardiotonic Agents; D007378:Interleukins; D011412:Propanolamines; D011799:Quinazolines; D000077261:Carvedilol; D008315:Malondialdehyde; C018176:bunazosin; D013482:Superoxide Dismutase; D008790:Metoprolol