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 th e supernatants of Trypanosoma cruzi-infected human umbilical vein endo thelial cells (HUVEC). Infection of HUVEC and vascular smooth muscle c ells had no effect on the synthesis of transforming growth factor-beta , which induces ET-1 synthesis. Bioassay studies of isolated rat aorti c rings revealed that the increases in ET-1 production were associated with augmented contractile responses, which were significantly attenu ated by preincubation with the ET, receptor antagonist, BQ-123. When b ig ET was incubated with the parasite, there was no conversion of the precursor to the active hormone (ET-1), demonstrating that the parasit e did not possess the necessary converting enzyme. These observations suggest the potential importance of ET-1 in the etiology of the microv ascular spasm associated with Chagas' disease.