Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone

H. B. Tanowitz, M. Wittner, S. A. Morris, L. M. Weiss, S. A. Douglas, M. Spektor, G. J. Christ

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Abstract

Microvascular compromise is an important cause of Trypanosoma cruzi-induced heart disease which is reversed by verapamil (VER). Using human umbilical vein endothelial cells (HUVECs) infected with T.cruzi we studied the mechanism of parasite-induced alterations in vascular tone. T. cruzi infection caused an increased concentration of endothelin-1 ([ET-1]) in the supernatants of T. cruzi-infected cells. A rat aortic ring model, denuded of endothelial cells, was used to study the significance of this observation. Rings incubated with supernatants of infected HUVECs exhibited a significant increase in the magnitude of the steady-state contractile response (grams of tension), that was inhibited ≈50% by the ETA antagonist BMS-182,874 or BQ-123. When HUVECs were incubated with VER prior to infection there was no effect on the synthesis of ET-1, however, there was a significant diminution in the observed contractile response of the aortic rings. When HUVECs were incubated with VER post-infection, a similar reduction in tension development was observed. Preincubation of fura-2 loaded cultured human vascular smooth muscle cells with VER resulted in a significant diminution in the peak amplitude of the ET-1-induced intracellular calcium transient. Finally, preincubation of HUVECs with phosphoramidon (PR) (inhibitor of endothelin converting enzyme), prior to infection, produced a significant reduction in [ET-1]. Aortic rings exposed to these PR-pretreated supernatants exhibited a corresponding diminution in the magnitude of the steady-state contractile response relative to control responses in the absence of PR-pretreatment. These data demonstrate that the vasoconstriction associated with T.cruzi infection is a result, in part, of the effects of ET-1.

Original languageEnglish (US)
Pages (from-to)A504
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Tanowitz, H. B., Wittner, M., Morris, S. A., Weiss, L. M., Douglas, S. A., Spektor, M., & Christ, G. J. (1997). Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone. FASEB Journal, 11(3), A504.