Protective role of ETA endothelin receptors during the acute phase of Trypanosoma cruzi infection in rats

Camargos, Elizabeth R.S.; Rocha, Lamara Laguardia Valente; Rachid, Milene Alvarenga; Almeida, Alvair P.; Ferreira, Anderson J.; Teixeira-Jr, Antônio Lúcio; Chiari, Égler; Barton, Matthias; Teixeira, Mauro Martins; Machado, Conceição R. S.

doi:10.1016/j.micinf.2004.03.002

Cited by 19 publications

(14 citation statements)

References 32 publications

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“…All of these pathways are crucial in the development of cardiovascular dysfunction. Previous observations from our laboratory and others have implicated ET-1 in the vasculopathy associated with T. cruzi infection (2,31,32,52,57).…”

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confidence: 64%

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Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease

Tanowitz¹,

Huang²,

Jelicks

et al. 2005

Infect Immun

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confidence: 64%

“…Recent evidence suggests that ET-1 contributes to the pathogenesis of Chagasic cardiomyopathy (2,31,32,35,36). We had previously demonstrated that treatment of T. cruzi-infected mice with phosphoramidon, a nonspecific ECE inhibitor, ameliorated chronic cardiomyopathy (15).…”

Section: Discussionmentioning

confidence: 94%

Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease

Tanowitz¹,

Huang²,

Jelicks

et al. 2005

Infect Immun

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“…Moreover, the compound was unable to enhance the killing mediated by a suboptimal concentration of IFN-γ (1 U/mL). For comparison, treatment with IFN-γ (100 U/mL) greatly enhanced the killing of T. cruzi by peritoneal macrophages Endothelin-1 receptor antagonist in acute T. cruzi infection www.bjournal.com.br gesting that these receptors in fact play a role in the defense against T. cruzi (14,15,17). However, we also used BSF461314, an ET A receptor antagonist, in T. cruzi-infected mice and did not find changes in parasitemia or parasitism (Roffê E, Souza ALS, Machado PP, Barcelos LS, Romanha AJ, Mariano FS, Silva JS, Machado CR, Tanowitz HB, Teixeira MM, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…An increase of myocardial parasite load and inflammation was observed also in rats treated with the ET A/B receptor antagonist bosentan (16). These findings suggest that ET-1 is part of a cascade of events leading to a protective immune response against acute T. cruzi infection in rats (14)(15)(16). However, the role of ET-1 in the ability of the host to deal with infection has not been determined in any other species.…”

Section: Introductionmentioning

confidence: 95%

“…In T. cruzi-infected mice, treatment with phosphoramidon, an endothelinconverting enzyme and neutral endopeptidase inhibitor, and verapamil, a first generation L-type calcium channel antagonist, reduced or abrogated mortality and attenuated cardiac pathology and dysfunction parameters (10)(11)(12)(13). Similarly, treatment with BSF461314, an ET A receptor antagonist, was able to prevent changes in coronary flow in T. cruzi-infected rats (14,15). In the latter studies, ET A receptor antagonist treatment was associated with enhanced parasitemia, inflammation and parasitism in myocardium and diaphragm.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice

Roffê

Souza

Machado

et al. 2007

Braz J Med Biol Res

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Chagas' disease, caused by the protozoan Trypanosoma cruzi, is a major cause of cardiovascular disability in countries where it is endemic. Damage to the heart microvasculature has been proposed to be an important factor in the pathogenesis of heart dysfunction. Endothelin-1 (ET-1) is a potent vasoconstrictor and exerts its effects via specific ET A and ET B receptors. A few studies have suggested a role for ET-1 and its receptors in the pathogenesis of Chagas' disease. We investigated the effects of treatment with bosentan, an ET A /ET B receptor antagonist, on the course of T. cruzi infection (Y strain) in C57Bl/6 mice. Treatment with bosentan (100 mg kg -1 day -1 ) was given per os starting day 0 after infection until sacrifice. Bosentan significantly increased myocardial inflammation, with no effects on parasitemia. Although the total number of nests was similar, a lower number of intact amastigote nests was found in the heart of bosentan-treated animals. Bosentan failed to affect the infection-associated increase in the cardiac levels of the cytokines IFN-γ and TNF-α and the chemokines CCL2/MCP-1, CCL3/MIP-1α and CCL5/RANTES. In vitro, pre-incubation with ET-1 (0.1 µM) 4 h before infection enhanced the uptake of the parasites by peritoneal macrophages, and this effect was abrogated when macrophages were pre-treated with bosentan (1 µM) 15 min before incubation with ET-1. However, ET-1 did not alter killing of intracellular parasites after 48 h of in vitro infection. Our data suggest that bosentan-treated mice have a delay in controlling parasitism which is compensated for exacerbated inflammation. Infection is eventually controlled in these animals and lethality is unchanged, demonstrating that ET-1 plays a minor role in the protection against acute murine T. cruzi infection.

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Inflammation and Chagas Disease

Talvani

Teixeira

2011

Advances in Parasitology

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Protective role of ETA endothelin receptors during the acute phase of Trypanosoma cruzi infection in rats

Cited by 19 publications

References 32 publications

Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease

Role of Endothelin 1 in the Pathogenesis of Chronic Chagasic Heart Disease

Endothelin-1 receptors play a minor role in the protection against acute Trypanosoma cruzi infection in mice

Inflammation and Chagas Disease

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