An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats

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Title
An inhibitor of inducible nitric oxide synthase ameliorates experimental autoimmune myocarditis in Lewis rats
Author(s)
Tae Kyun Shin; Naoyuki Tanuma; Seung Joon Kim; Jae Kwang Jin; Chang Jong Moon; Ki Ok Kim; Kuniko Kohyama; Yoh Matsumoto; Byung Hwa Hyun
Bibliographic Citation
Journal of Neuroimmunology, vol. 92, pp. 133-138
Publication Year
1998
Abstract
We studied the effect of nitric oxide (NO) on experimental autoimmune myocarditis (EAC) in rats. We examined the role of inducible nitric oxide synthase (iNOS), an enzyme that produces NO, on hearts affected with EAC, by testing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissues, but not in CFA immunized cases. Immunohistochemically, the majority of ED1+ macrophages in the EAC lesions were positive for iNOS and nitrotyrosine. A high dose of AG (200 mg/kg/day) significantly reduced the incidence of EAC (p < 0.05) and ameliorated the histological score for the cardiac inflammation (p < 0.01) compared with the low dose AG (100 mg/kg/day) and vehicle treated groups. The immunoblot analysis showed that a high dose of AG effectively suppressed iNOS in hearts affected with EAC. An iNOS band was barely detected in the high dose AG (200 mg/kg) treated group, while it was distinctively visualized in the vehicle and low dose AG (100 mg/kg) treated groups. These results suggest that iNOS is upregulated in EAC lesions and increased NO production plays an important role in the development of EAC. In addition, selective iNOS inhibitors may have a therapeutic role in treating certain autoimmune diseases including EAC.
Keyword
Experimental autoimmune myocarditisNitric oxide synthaseAminoguanidine
ISSN
0165-5728
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/S0165-5728(98)00194-5
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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