Protective role of ETA endothelin receptors during the acute phase of Trypanosoma cruzi infection in rats.
Chagas' disease, caused by Trypanosoma cruzi, has an acute phase characterized by blood-circulating trypomastigotes and amastigote proliferation in several cell types, especially muscle cells. In the chronic phase, around 70% of infected people are asymptomatic (latent form). The remainder develop chagasic cardiomyopathy and/or digestive syndromes. There is evidence for aggravation of the chronic cardiac pathology by endothelin-mediated vasoconstriction. Holtzman rats have proven to be a good model for Chagas' disease acute phase and latent chronic phase. Now, we investigate the effects of prolonged treatment with an endothelin ET(A) receptor antagonist, BSF 461314, during the acute phase on parasitemia, coronary flow, tissue parasitism and the inflammatory process. Using isolated heart in Langendorff's preparation, endothelial dysfunction was observed only in non-treated infected animals. Histoquantitative analyses carried out in heart and diaphragm showed higher tissue parasitism and/or inflammatory process in BSF 461314-treated animals. Our data indicate that endothelin ET(A) receptors contribute to the initial mechanisms of parasite control. Impairment of the endothelium-dependent vasodilatation favors hazardous effects. However, blocking endothelin ET(A) receptors can prevent the latter.
Camargos
Elizabeth R S
ER
Departamento de Morfologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Av. Antonio Carlos 6627, P.O. Box 486, CEP: 31270-901 Belo Horizonte, MG, Brazil.
Rocha
Lamara L V
LL
Rachid
Milene A
MA
Almeida
Alvair P
AP
Ferreira
Anderson J
AJ
Teixeira
Antonio L
AL
Chiari
Egler
E
Barton
Matthias
M
Teixeira
Mauro M
MM
Machado
Conceição R S
CR
D000208:Acute Disease; D000818:Animals; D001783:Blood Flow Velocity; D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control*; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D006321:Heart / Q000469:parasitology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D008297:Male; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology / Q000517:prevention & control; D010666:Phenylpropionates / Q000737:chemistry / Q000627:therapeutic use; D011743:Pyrimidines / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism*; D014349:Trypanosoma cruzi
D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011743:Pyrimidines; D044022:Receptor, Endothelin A; C107831:darusentan