Avaliação dos mecanismos envolvidos nas alterações vasculares em camundongos infectados pela cepa colombiana de trypanossoma cruzi

Abstract

The infection by Trypanosoma Cruzi causes Chagas disease. The disease results in acute myocarditis and chronic cardiomyopathy, both associated with microvascular injury. Although vascular dysfunction is present in the vessels of the cardiac microvasculature, little or nothing is known about the underlying mechanism of this dysfunction in other vascular beds. The aim of this study was to evaluate whether the Colombian strain of T. Cruzi affects, directly or indirectly, systemic vascular function. Eight weeks old C57BL6 male mice were infected with the Colombian strain of T. Cruzi. The animals were used for the experiments 30 days after infection. Immunofluorescence experiments showed the presence of the antigen TcRBP28, of the Colombian strain of T. Cruzi, in the endothelial layer of the aorta of infected animals. Regarding the vascular response was observed in aorta of infected animals, a decrease in the vasorelaxant response accompanied by decreased expression of total eNOS, a reduction in phosphorylation of the activation site of the enzyme (eNOS Ser1177), concomitant with an increase in phosphorylation of inactivation site (eNOSThr495). However, the basal NO production was markedly increased in infected animals, as well as the expression of iNOS. There was also an increase in contractile response in aortic rings from infected animals. The increased contraction was not reversed by bosentan antagonist of ET- 1 receptors. Ibuprofen, a non-selective COX inhibitor, SQ28668, a TXA2 receptor antagonist and removal of the endothelium normalized the contractile response of infected animals, indicating that TXA2 is involved in the increase in contraction. Our data of fluorescence microscopy showed an increase in superoxide production and increased expression of nitrotyrosine. Tiron, a scavenger of superoxide and SOD, an enzyme that degrades superoxide, also normalized the contractile response of infected animals. TNF-α, was greatly increased in the serum of infected animals, suggesting the existence of systemic inflammation. Together our results, allows us to conclude that the presence of the parasite in aortic endothelial cells of mice and systemic inflammation, cause a vascular dysfunction, probably by a decreased expression and function of eNOS and by increasing iNOS expression. Reactive species of oxygen and nitrogen are formed installing a frame of oxidative stress, which associated with increased levels of TXA2 causes increased contractile response.