Key result
Treatment with the ET(A) receptor antagonist BSF-461314 markedly increased parasitaemia and parasite nests in heart tissue, but prevented changes in coronary flow induced by T. cruzi infection.
Why the study?
Does the ET(A) receptor antagonist BSF-461314 alter parasitaemia and coronary blood flow in rats with acute Trypanosoma cruzi infection?
Does the ET(A) receptor antagonist BSF-461314 alter parasitaemia and coronary blood flow in rats with acute Trypanosoma cruzi infection?
Endothelin-1 contributes to the protective immune response against acute T. cruzi infection but also mediates impaired endothelium-dependent vasomotion in the coronary microcirculation.
ET(A) antagonism may heighten parasitaemia despite vascular protection in acute Chagas models; leaves open net benefit for human infection.
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.
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Camargos et al. (2002) studied Trypanosoma cruzi acute infection (Chagas' disease). BSF-461314 (ET(A) receptor antagonist) was evaluated on Parasitaemia, histopathological analysis of heart tissue, and coronary blood flow. Treatment with the ET(A) receptor antagonist BSF-461314 markedly increased parasitaemia and parasite nests in heart tissue, but prevented changes in coronary flow induced by T. cruzi infection.
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