© 1997 American Heart Association, Inc.
Articles |
Low-Dose N
-Nitro-L-Arginine Methyl Ester Treatment Improves Survival Rate and Decreases Myocardial Injury in a Murine Model of Viral Myocarditis Induced by Coxsackievirus B3
From the First Department of Internal Medicine (S.M., S.K., K.K., K.H., M.Y.), the Department of Microbiology (H.H.), and the First Department of Pathology (Y.H., H.I.), Kobe (Japan) University School of Medicine.
Correspondence to Seinosuke Kawashima, MD, First Department of Internal Medicine, Kobe University School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650 Japan.
Abstract Recent reports demonstrated the expression of
inducible-type NO synthase in the heart of viral myocarditis. Since NO
has multiple biological actions, a substantial amount of NO produced in
the diseased heart may act either as a cytotoxic or as a cytoprotective
molecule in the process of myocarditis. In the present study, we
examined the effect of inhibition of NO synthesis on the mortality and
the extent of myocardial injury in a murine model of coxsackievirus
B3–induced myocarditis. We fed the infected mice drinking water
containing a relatively low concentration (0.37 mmol/L) of
N-nitro-L-arginine methyl ester
(L-NAME) for 14 days after virus inoculation. This dose of L-NAME did
not change virus titers in the heart. However, L-NAME–fed mice showed
a significant reduction in mortality compared with those fed normal
drinking water (nontreated mice). On the contrary, mice given a higher
concentration of L-NAME (3.7 mmol/L) exhibited increased
mortality. In addition, mice fed a low concentration of L-NAME showed
reductions in the severity of heart failure and in the area of
myocardial necrosis. Although systemic blood pressure was reduced in
nontreated mice, in mice fed a low concentration of L-NAME, it was
maintained at a level similar to that in uninfected control mice.
L-NAME–treated mice also exhibited a reduction in the degree of
inflammatory cell infiltration associated with decreased
production of tissue prostaglandin E2
levels in the heart compared with nontreated mice. Therefore, NO is
likely to be involved in the pathogenic mechanisms of myocardial injury
and resultant cardiac dysfunction in a murine model of coxsackievirus
B3–induced viral myocarditis.
Key Words: N-nitro-L-arginine methyl ester • nitric oxide • viral myocarditis • prostaglandin
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