Skip Navigation

Cardiovascular Research 1999 43(2):389-397; doi:10.1016/S0008-6363(99)00105-4
© 1999 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Ishiyama, S.
Right arrow Articles by Marumo, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ishiyama, S.
Right arrow Articles by Marumo, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1999, European Society of Cardiology

Inhibitory effects of vesnarinone in the progression of myocardial damage in experimental autoimmune myocarditis in rats

Shigeru Ishiyamaa, Michiaki Hiroeb,*, Toshio Nishikawaa, Takashi Shimojob, Tetsumi Hosokawac, Ikuo Ikedaa, Tetsuya Toyozakid, Takeshi Kasajimaa and Fumiaki Marumob

aDepartment of Pathology, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan
bSecond Department of Internal Medicine, Tokyo Medical & Dental University, Tokyo, Japan
cOtsuka Pharmaceutical Co., Ltd., Tokushima, Japan
dThe Division of Pathology, Institute of Pulmonary Cancer Research, Chiba University, School of Medicine, Chiba, Japan

* Corresponding author. Tel.: +81-3-5803-5214; fax: +81-3-5803-0132

Objectives: Vesnarinone, a positive inotropic and immunomodulatory agent, diminishes nitric oxide (NO) levels by suppressing the induction of inducible NO synthase (iNOS) expressed in cytokine-stimulated macrophages and cardiomyocytes. We examined whether vesnarinone exerts inhibitory effects on the progression of myocardial damage in experimental autoimmune myocarditis in rats through suppression of iNOS. Methods: Myocarditis was induced in 30 Lewis rats by injection of porcine cardiac myosin and vesnarinone was orally administered to 20 of the 30 rats. On day 21 after immunization (the climax of inflammation), the hemodynamics were examined and the severity of myocarditis was evaluated by determining the area ratio (%) [affected/entire area] of myocardial lesions in histological sections. Levels of serum CK-MB, NOx (NO2–+NO3–), TNF-{alpha} and IL-1β, and cyclic GMP, iNOS mRNA, TNF-{alpha} and IL-1β in heart tissues were determined. Expression of iNOS and TNF-{alpha} protein were examined by immunohistochemical methods. Results: Histopathological examination revealed extensive myocardial destruction and massive infiltration of inflammatory cells in the vesnarinone-untreated rats. The area ratio of the lesions in the treated rats was significantly lower than that in the untreated ones. Levels of CK-MB, NOx, cyclic GMP, cytokines and iNOS mRNA were significantly lower in the vesnarinone-treated rats. Infiltrating macrophages and cardiomyocytes in the untreated rats showed much higher levels of expression of iNOS and TNF-{alpha} than those in the vesnarinone-treated rats. Conclusions: Vesnarinone may prove to be useful in the treatment of myocarditis by attenuating NO production through suppression of iNOS induced by cytokines.

KEYWORDS Myocarditis; Vesnarinone; Nitric oxide; Inducible nitric oxide synthase; Proinflammatory cytokines


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.