title: Protective effects of losartan in mice with chronic viral myocarditis induced by coxsackievirus B3.
abstract: OBJECTIVE
  To investigate whether losartan has protective effects in mice with chronic viral myocarditis induced by coxsackievirus B3 (CVB3).
  
  
  METHODS
  Thirty two male Balb/c mice were intraperitoneally injected with CVB3 (10×TCID50) to induce chronic viral myocarditis (CVM). Losartan at 12.5mg/kg (n=16) or normal saline (n=16) were orally administered daily for 28 days to these mice. Uninfected mice (n=6) were used as controls. On day 29, all mice underwent anesthesia and echocardiography prior to sacrifice. Serum IL-17, IL-4, IFN-γ and TNF-α levels were measured by enzyme-linked immunosorbent assay, and cardiac tissues were histologically examined after hematoxylin & eosin staining. In addition, the effect of losartan on the virus titers in primary cultured neonatal rat cardiomyocytes infected with CVB3 was measured on Hep-2 cells at 72 h post infection.
  
  
  RESULTS
  Mice infected with CBV3 had significantly increased mortality, heart/body weight ratios, necrosis and inflammatory scores and decreased cardiac ejection fractions, compared with the controls (all P<0.05). Losartan significantly decreased mortality from 40.0% to 12.5%, heart/body weight ratios from 7.08 ± 2.17 to 4.15 ± 0.99, and necrosis and inflammatory scores from 3.33 ± 0.50 to 2.50 ± 0.65 (all P<0.05), and increased ejection fractions from 55.80 ± 9.25 to 72.31 ± 12.15 (P<0.05). Losartan significantly enhanced IL-4, and decreased IFN-γ, TNF-α and IL-17 (all P<0.05). In the in vitro experiment, losartan had no influence on virus titers.
  
  
  CONCLUSIONS
  Losartan protects mice against CVB3-induced CVM, most likely through upregulating Th2 responses, and down-regulating Th1 and Th17 responses.
authors.affiliation: Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu 610041, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.forename: Jin-Nan
authors.initials: JN
authors.lastname: Li
authors.forename: Harry Hua-Xiang
authors.initials: HH
authors.lastname: Xia
authors.forename: Shi-Lun
authors.initials: SL
authors.lastname: Zhang
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhong
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Wu
authors.forename: Shi-Kun
authors.initials: SK
authors.lastname: Miao
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000998:Antiviral Agents / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D003384:Coxsackievirus Infections / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D029822:Enterovirus B, Human / Q000187:drug effects*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011991:Receptors, Virus
chemical_list: D000998:Antiviral Agents; D002316:Cardiotonic Agents; D011991:Receptors, Virus; C105941:coxsackievirus B receptor; D019808:Losartan