TRYPANOSOMA-CRUZI INDUCES ENDOTHELIN RELEASE FROM ENDOTHELIAL-CELLS

The potential role of endothelin-1 (ET-1) in the pathogenesis of focal microvascular spasm, previously implicated in the etiology of Chagas' cardiomyopathy, was investigated. There was an increase in ET-1 in the supernatants of Trypanosoma cruzi-infected human umbilical vein endothelial cells (HUVEC). Infection of HUVEC and vascular smooth muscle cells had no effect on the synthesis of transforming growth factor-beta, which induces ET-1 synthesis. Bioassay studies of isolated rat aortic rings revealed that the increases in ET-1 production were associated with augmented contractile responses, which were significantly attenuated by preincubation with the ET, receptor antagonist, BQ-123. When big ET was incubated with the parasite, there was no conversion of the precursor to the active hormone (ET-1), demonstrating that the parasite did not possess the necessary converting enzyme. These observations suggest the potential importance of ET-1 in the etiology of the microvascular spasm associated with Chagas' disease.