The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi

Herbert B. Tanowitz, Murray Wittner, Stephen A. Morris, Weixin Zhao, Louis M. Weiss, Victor B. Hatcher, Vicki L. Braunstein, Huan Huang, Stephen A. Douglas, Mira Valcic, Mariya Spektor, George J. Christ

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of heart disease in Latin America. T. cruzi-induced microvascular compromise, in turn, is thought to play a major role in chagasic heart disease. Previous in vitro studies have implicated endothelin-1 (ET-1) as a potentially important vasomodulator present in increased levels in the supernatant of T. cruzi infected cultured human umbilical vein endothelial cells (HUVEC). Thus, the goal of the present investigation was to further evaluate the potentially important contribution of ET-1 to T cruzi-induced alterations in vascular tone in vitro. Bioassay studies once again documented that exposure of isolated rat aortic rings to infected HUVEC supernatants elicited contractile responses whose steady-state magnitude was significantly greater than contractile responses elicited by exposure of aortic rings to uninfected HUVEC supernatants. Furthermore, the increased aortic contractility was significantly attenuated by the presence of the ETA subtype selective antagonists BMS-182,874 or BQ-123. Additionally, incubation of HUVEC with either verapamil or phosphoramidon prior to infection was also associated with reduced aortic contractility, upon exposure to the supernatant. Phosphoramidon, but not verapamil, produced a significant decrease in the measured ET-1 levels in the HUVEC supernatant. Consistent with the bioassay results, preincubation of Fura-2-loaded cultured rat aortic vascular smooth muscle cells with verapamil resulted in a near complete ablation of ET-1-induced transmembrane Ca2+ flux. Taken together, these data are consistent with the hypothesis that ET-1-induced vasoconstriction may play an important modulatory role in the vascular compromise characteristic of T. cruzi infection.

Original languageEnglish (US)
Pages (from-to)217-230
Number of pages14
JournalEndothelium: Journal of Endothelial Cell Research
Volume6
Issue number3
DOIs
StatePublished - Jan 1 1999

Keywords

  • Chagas' disease
  • Endothelial cells
  • Endothelin
  • Phosphoramidon
  • Trypanosoma cruzi
  • Vascular smooth muscle cells
  • Verapamil

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Fingerprint Dive into the research topics of 'The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi'. Together they form a unique fingerprint.

  • Cite this