N -Acetylcysteine Ameliorates Experimental Autoimmune Myocarditis in Rats via Nitric Oxide

BACKGROUND: Oxidative stress may play an important role in the development of myocarditis. We investigated the effects of N-acetylcysteine (NAC), a potent antioxidant, on experimental autoimmune myocarditis (EAM) in rats. METHODS AND RESULTS: A rat model of porcine myosin-induced EAM was used. After the immunization with myosin, NAC (20 mg/kg/d) or saline was injected intraperitoneally on days 1 to 21. Additional myosin-immunized rats treated with NAC were orally given 25 mg/kg/d of N(G)-nitro-l-arginine methylester (l-NAME), an inhibitor of nitric oxide (NO) synthase, and N(G)-nitro-d-arginine methylester (d-NAME), an inactive enantiomer. The NAC treatment improved cardiac pathology associated with reduced superoxide production. In the EAM rats treated with NAC associated with oral l-NAME, but not with oral d-NAME, the severity of myocarditis was not reduced. Expression of intercellular adhesion molecule 1 was reduced by NAC treatment. Myocardial c-kit(+) cells were demonstrated only in the NAC-treated group. Hemodynamic study showed that the increased left ventricular mass produced by myocardial inflammation tended to be reduced by NAC treatment. CONCLUSION: Treatment with NAC ameliorated myocardial injury via NO system in a rat model of myocarditis.