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 ETA 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.
Wittner
M
M
Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Christ
G J
GJ
Huang
H
H
Weiss
L M
LM
Hatcher
V B
VB
Morris
S A
SA
Orr
G A
GA
Berman
J W
JW
Zeballos
G A
GA
Douglas
S A
SA
D000818:Animals; D001011:Aorta / Q000502:physiology; D001483:Base Sequence; D001681:Biological Assay; D002478:Cells, Cultured; D019332:Endothelin-1; D016232:Endothelins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000469:parasitology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000469:parasitology; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014349:Trypanosoma cruzi / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta