Nitric Oxide Synthase in Experimental Autoimmune Myocarditis Dysfunction

This study reports the expression of inducible nitric oxide synthase (NOS) in heart from autoimmune myocarditis mice associated with an alteration in their contractile behavior. By mean of the production of [U−14C]citrulline from [U−14C]arginine and immunoblot assay, the expression of iNOS was demonstrated in autoimmune atria that was normally absent. The iNOS activity decreased with administration of dexametasone and in mice treated with monoclonal anti-interferon-γantibody (anti-IFN-γmAb). The inhibitors of protein kinase C activity (staurosporine) but not calcium/calmodulin (trifluoperazine) attenuated the iNOS activity. Moreover, autoimmune atria presented contractile alterations (lower values of dF/dtthan control). Thein vivotreatment with inhibitors of NOS activity or anti-IFN-γmAb or dexametasone improved the contractile activity of autoimmune atria with no change in the contractility of normal atria. The results suggest that the infiltrative cells in myocarditis heart have a potential role in cardiac dysfunction by production of IFN-γand subsequent expression of iNOS, that in turn alter the contractile behavior of the heart. The data indicate that cytokines induced activation of -arginine nitric oxide pathway in myocarditis atria leading to contractile dysfunction.