Efeitos benéficos dos tratamentos de restrição às ações da angiotensina II na infecção experimental pelo Trypanosoma cruzi.

Chagas heart disease (CHD) is the most important clinical manifestation of Trypanosoma cruzi infection and presents variable clinical course from asymptomatic to severe form of heart failure. Drugs previously used to improve functional capacity or mitigate cardiac remodeling in CHD (eg. inhibitors of angiotensin converting enzyme – ACE) have also presented actions on inflammatory mechanisms, a sine qua non condition for the pathogenesis of CHD. In this study, we evaluated the single and combined action of Enalapril (ACE inhibitor) and Losartan (angiotensin II receptor blocker) during the acute inflammatory phase of experimental Chagas disease. Swiss mice were infected with tripomastigotes forms of “Colombian” strain of T. cruzi and treated daily for 30 days with three different doses of Enalapril (10, 15 and 25mg/Kg), Losartan (10, 15 and 20mg/Kg) and combinations of Enalapril + Losartan (10 +10, 15 + 10, 10 + 15 and 15 + 15mg/Kg). Parasitemia and survival rate was used to select the best dose of drugs (Enalapril – 25mg/Kg, Losartan – 15mg/Kg and combination of both – 15mg/Kg each). In a 2nd phase, C57BL/6 mice were infected with the same strain of T. cruzi and treated for 20 days with drugs described, besides benznidazole (100 mg/Kg) and vehicle (untreated control). After 22 days of infection, the animals were euthanized to collect biological samples. It was observed a reduction of blood and tissue parasites load in animals treated with Losartan or Enalapril, but not to the combination of both. Serum levels of inflammatory mediators TNF-alpha, CCL2 and CCL5 were reduced to those Losartan-treated animals which also showed an increase of IL-17 and IL-10 levels. Treatment with Enalapril leads to a reduction of TNF-alpha, IL-17 and CCL5, but maintained IL-10 and CCL2 serum levels. For the immunoassays, treatment with the combination showed similar results to those observed for Enalapril. All treatments showed a reduction in cardiac inflammation in histomorphometric analysis. Our data showed pleiotropic effects of treatments with the monotherapies of drugs which restrict the actions of Angio II through the interference of parasite replication and immune response modulation, culminating in the reduction of the inflammatory infiltrate in cardiac muscle tissue. Together, these findings suggest that these treatments can lead to a protection of heart damage mediated by immune response during acute experimental T. cruzi infection.