This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mikami, S. Articles by Yokoyama, M. Search for Related Content PubMed PubMed Citation Articles by Mikami, S. Articles by Yokoyama, M.

(Circulation Research. 1997;81:504-511.)
© 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

Shuji Mikami, Seinosuke Kawashima, Kenji Kanazawa, Ken-ichi Hirata, Hak Hotta, Yoshitake Hayashi, Hiroshi Itoh, , Mitsuhiro Yokoyama

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

This article has been cited by other articles:

				J. W. Magnani and G. W. Dec Myocarditis: Current Trends in Diagnosis and Treatment Circulation, February 14, 2006; 113(6): 876 - 890. [Full Text] [PDF]

				R. Morita, T. Uchiyama, and T. Hori Nitric Oxide Inhibits IFN-{alpha} Production of Human Plasmacytoid Dendritic Cells Partly via a Guanosine 3',5'-Cyclic Monophosphate-Dependent Pathway J. Immunol., July 15, 2005; 175(2): 806 - 812. [Abstract] [Full Text] [PDF]

				B.-K. Lim, S.-C. Choe, J.-O. Shin, S.-H. Ho, J.-M. Kim, S.-S. Yu, S. Kim, and E.-S. Jeon Local Expression of Interleukin-1 Receptor Antagonist by Plasmid DNA Improves Mortality and Decreases Myocardial Inflammation in Experimental Coxsackieviral Myocarditis Circulation, March 19, 2002; 105(11): 1278 - 1281. [Abstract] [Full Text] [PDF]

				V. A. Peotta, E. C. Vasquez, and S. S. Meyrelles Cardiovascular Neural Reflexes in L-NAME-Induced Hypertension in Mice Hypertension, September 1, 2001; 38(3): 555 - 559. [Abstract] [Full Text] [PDF]

				A. M. Feldman and D. McNamara Myocarditis N. Engl. J. Med., November 9, 2000; 343(19): 1388 - 1398. [Full Text] [PDF]

				C. Zaragoza, C. J. Ocampo, M. Saura, C. Bao, M. Leppo, A. Lafond-Walker, D. R. Thiemann, R. Hruban, and C. J. Lowenstein Inducible Nitric Oxide Synthase Protection Against Coxsackievirus Pancreatitis J. Immunol., November 15, 1999; 163(10): 5497 - 5504. [Abstract] [Full Text] [PDF]

				K. Ono, A. Matsumori, T. Shioi, Y. Furukawa, and S. Sasayama Contribution of Endothelin-1 to Myocardial Injury in a Murine Model of Myocarditis : Acute Effects of Bosentan, an Endothelin Receptor Antagonist Circulation, October 26, 1999; 100(17): 1823 - 1829. [Abstract] [Full Text] [PDF]

				C. Zaragoza, C. Ocampo, M. Saura, M. Leppo, X.-Q. Wei, R. Quick, S. Moncada, F. Y. Liew, and C. J. Lowenstein The role of inducible nitric oxide synthase in the host response to Coxsackievirus myocarditis PNAS, March 3, 1998; 95(5): 2469 - 2474. [Abstract] [Full Text] [PDF]