Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone

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

Research output: Contribution to journalArticle

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)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - 1997
Externally publishedYes

Fingerprint

endothelins
Trypanosoma cruzi
Endothelial cells
Human Umbilical Vein Endothelial Cells
Endothelin-1
blood vessels
Blood Vessels
Verapamil
verapamil
Infection
infection
Fura-2
Vasoconstriction
vasoconstriction
Vascular Smooth Muscle
Endothelins
heart diseases
Smooth Muscle Myocytes
Heart Diseases
Parasites

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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).

Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone. / Tanowitz, H. B.; Wittner, M.; Morris, S. A.; Weiss, Louis M.; Douglas, S. A.; Spektor, M.; Christ, G. J.

In: FASEB Journal, Vol. 11, No. 3, 1997.

Research output: Contribution to journalArticle

Tanowitz, HB, Wittner, M, Morris, SA, Weiss, LM, Douglas, SA, Spektor, M & Christ, GJ 1997, 'Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone', FASEB Journal, vol. 11, no. 3.
Tanowitz HB, Wittner M, Morris SA, Weiss LM, Douglas SA, Spektor M et al. Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone. FASEB Journal. 1997;11(3).
Tanowitz, H. B. ; Wittner, M. ; Morris, S. A. ; Weiss, Louis M. ; Douglas, S. A. ; Spektor, M. ; Christ, G. J. / Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone. In: FASEB Journal. 1997 ; Vol. 11, No. 3.
@article{ff2206268792468db09801bb195145a9,
title = "Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone",
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.",
author = "Tanowitz, {H. B.} and M. Wittner and Morris, {S. A.} and Weiss, {Louis M.} and Douglas, {S. A.} and M. Spektor and Christ, {G. J.}",
year = "1997",
language = "English (US)",
volume = "11",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - Mechanistic basis of trypanosoma cruzi induced alterations in vascular tone

AU - Tanowitz, H. B.

AU - Wittner, M.

AU - Morris, S. A.

AU - Weiss, Louis M.

AU - Douglas, S. A.

AU - Spektor, M.

AU - Christ, G. J.

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33750239250&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750239250&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750239250

VL - 11

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -