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

We studied the effect of nitric oxide (NO) on experimental autoimmune myoca rditis (EAC) in rats. We examined the role of inducible nitric oxide syntha se (iNOS), an enzyme that produces NO, on hearts affected with EAC, by test ing the effects of aminoguanidine (AG), a selective iNOS inhibitor, on the course of EAC. Western blotting detected iNOS in the affected cardiac tissu es, but not in CFA immunized cases. Immunohistochemically, the majority of ED1(+) macrophages in the EAC lesions were positive for iNOS and nitrotyros ine. 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 in flammation (p < 0.01) compared with the low dose AG (100 mg/kg/day) and veh icle treated groups. The immunoblot analysis showed that a high dose of AG effectively suppressed iNOS in hearts affected with EAC. An iNOS band was b arely 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 treat ing certain autoimmune diseases including EAC. (C) 1998 Elsevier Science B. V. All rights reserved.