Role of endothelin during experimental Trypanosoma cruzi infection in rats.
Chagas' disease is caused by the intracellular protozoan Trypanosoma cruzi. Here we have investigated the role of endothelin-1 in T. cruzi acute infection in rats, using the orally active ET(A) receptor antagonist BSF-461314. Treatment with BSF-461314 markedly increased parasitaemia, but animals managed to control the infection by day 15. Histopathological analysis of heart tissue at the end of the acute phase showed greater numbers of parasite nests in BSF-461314-treated animals. The perfusion of isolated rat hearts from infected animals with bradykinin failed to induce an increase, and actually reduced, coronary blood flow. Pretreatment with BSF-461314 prevented changes in coronary flow induced by T. cruzi infection. Together these results demonstrate that endothelin-1, through ET(A) receptor activation, contributes to the protective immune response against acute T. cruzi infection. Moreover, these data suggest that endothelin-1 is a mediator of impaired endothelium-dependent vasomotion in the coronary microcirculation associated with acute T. cruzi infection.
Camargos
Elizabeth R S
ER
Department of Morphology, Instituto de Ciências Biológicas, Federal University of Minas Gerais, Avenida Antônio Carlos 6627, Belo Horizonte, Minas Gerais, Brazil.
Machado
Conceição R S
CR
Teixeira
Antonio L
AL
Rocha
Lamara L V
LL
Ferreira
Anderson J
AJ
Almeida
Alvair P
AP
Barton
Matthias
M
Teixeira
Mauro M
MM
D000208:Acute Disease; D000818:Animals; D001920:Bradykinin; D002598:Chagas Cardiomyopathy / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006321:Heart / Q000469:parasitology; D008297:Male; D023421:Models, Animal; D018512:Parasitemia / Q000276:immunology / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents; D001920:Bradykinin