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 associa ted with myocardial dysfunction, including dysrhythmias, conduction di sturbances, and congestive heart failure. Nitric oxide (NO) has been i mplicated in the myocardial dysfunction associated with diseases of th e myocardium. The inducible form of nitric oxide synthase (iNOS) media tes 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 po stinfection with the Brazil strain of T. cruzi. Immunocytochemical sta ining 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 expre ssion in vivo. In addition, Northern blot analysis revealed that inter leukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA were induced during infection. These data suggest that the myocar dial cytokine-iNOS pathway may be an important factor in the pathogene sis of chagasic heart disease. In addition, this pathway may be a pote ntial target of future pharmacologic intervention. (C) 1997 by Elsevie r Science Inc.