Low-dose N omega-nitro-L-arginine methyl ester treatment improves survival rate and decreases myocardial injury in a murine model of viral myocarditis induced by coxsackievirus B3.
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 omega-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.
Mikami
S
S
First Department of Internal Medicine, University School of Medicine, Kobe, Japan.
Kawashima
S
S
Kanazawa
K
K
Hirata
K
K
Hotta
H
H
Hayashi
Y
Y
Itoh
H
H
Yokoyama
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D015232:Dinoprostone / Q000037:antagonists & inhibitors; D004770:Enterovirus / Q000302:isolation & purification; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006321:Heart / Q000821:virology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000821:virology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage* / Q000627:therapeutic use; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012016:Reference Values; D016019:Survival Analysis
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D015232:Dinoprostone; D019331:NG-Nitroarginine Methyl Ester