S. Ishiyama et al., Inhibitory effects of vesnarinone in the progression of myocardial damage in experimental autoimmune myocarditis in rats, CARDIO RES, 43(2), 1999, pp. 389-397
Citations number
28
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Objectives: Vesnarinone, a positive inotropic and immunomodulatory agent, d
iminishes nitric oxide (NO) levels by suppressing the induction of inducibl
e NO synthase (iNOS) expressed in cytokine-stimulated macrophages and cardi
omyocytes. 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 L
ewis rats by injection of porcine cardiac myosin and vesnarinone was orally
administered to 20 of the 30 rats. On day 21 after immunization (the clima
x of inflammation), the hemodynamics were examined and the severity of myoc
arditis was evaluated by determining the area ratio (%) [affected/entire ar
ea] of myocardial lesions in histological sections. Levels of serum CK-MB,
NOx (NO2- + NO3-), TNF-alpha and IL-1 beta, and cyclic GMP, iNOS mRNA, TNF-
alpha and IL-1 beta in heart tissues were determined. Expression of iNOS an
d 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 ra
ts. The area ratio of the lesions in the treated rats was significantly low
er than that in the untreated ones. Levels of CK-MB, NOx, cyclic GMP, cytok
ines 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 ve
snarinone-treated rats. Conclusions: Vesnarinone may prove to be useful in
the treatment of myocarditis by attenuating NO production through suppressi
on of iNOS induced by cytokines. (C) 1999 Elsevier Science B.V. All rights
reserved.