Trypanosoma cruzi infection induces myocardial nitric oxide synthase

Chagas' disease caused by Trypanosoma cruzi, is an important cause of myocarditis and cardiomyopathy. Acute and chronic infection is associated with myocardial dysfunction, including dysrhythmias, conduction disturbances, and congestive heart failure. Nitric oxide (NO) has been implicated in the myocardial dysfunction associated with diseases of the myocardium. The inducible form of nitric oxide synthase (iNOS) mediates the synthesis of NO and L-citrulline from L-arginine. An abundance of iNOS mRNA by Northern blot and a marked expression of iNOS protein by Western blot was demonstrated in the myocardium of mice 30 days postinfection with the Brazil strain of T. cruzi. Immunocytochemical staining of the myocardial sections from infected mice also revealed the expression of iNOS. Consistent with these observations, the myocardial L-citrulline content was higher in infected mice, confirming NO expression in vivo. In addition, Northern blot analysis revealed that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNA were induced during infection. These data suggest that the myocardial cytokine-iNOS pathway may be an important factor in the pathogenesis of chagasic heart disease. In addition, this pathway may be a potential target of future pharmacologic intervention.