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

被引:33
作者
Tanowitz, HB
Wittner, M
Morris, SA
Zhao, WX
Weiss, LM
Hatcher, VB
Braunstein, VL
Huang, H
Douglas, SA
Valcic, M
Spektor, M
Christ, GJ
机构
[1] Yeshiva Univ Albert Einstein Coll Med, Urol Lab Mol & Integrat Urol, Dept Urol, Bronx, NY 10461 USA
[2] Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA
[3] Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA
[4] Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA
[5] Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA
[6] SmithKline Beecham Pharmaceut, Dept Cardiovasc Pharmacol, King Of Prussia, PA 19406 USA
来源
ENDOTHELIUM-JOURNAL OF ENDOTHELIAL CELL RESEARCH | 1999年 / 6卷 / 03期
关键词
Chagas' disease; Trypanosoma cruzi; verapamil; endothelin; endothelial cells; vascular smooth muscle cells; phosphoramidon;
D O I
10.3109/10623329909053412
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-l-induced transmembrane Ca2+ flux. Taken together, these data are consistent with the hypothesis that ET-l-induced vasoconstriction may play an important modulatory role in the vascular compromise characteristic of T. cruzi infection.
引用
收藏
页码:217 / 230
页数:14
相关论文
共 64 条
[1]  
Barnes K, 1996, J CELL SCI, V109, P919
[2]  
BERGSMA DJ, 1995, ENDOTHELIN RECEPTORS, P37
[3]  
BONADONNA G, 1986, THROMB HAEMOSTASIS, V56, P308
[4]   Anti-peptide antibodies specific to rat endothelin-converting enzyme-1 isoforms reveal isoform localisation and expression [J].
Brown, CD ;
Barnes, K ;
Turner, AJ .
FEBS LETTERS, 1998, 424 (03) :183-187
[5]  
Christ G J, 1993, Int J Impot Res, V5, P77
[6]   DETERMINATION OF AGONIST DISSOCIATION-CONSTANTS IN ISOLATED VASCULATURE - EQUIVALENCE OF ESTIMATES OBTAINED BY THE METHOD OF PARTIAL IRREVERSIBLE RECEPTOR INACTIVATION AND A NOVEL APPLICATION OF THE OPERATIONAL MODEL OF PHARMACOLOGICAL AGONISM [J].
CHRIST, GJ .
LIFE SCIENCES, 1990, 47 (20) :1867-1874
[7]  
CHRIST GJ, 1991, J PHARMACOL EXP THER, V256, P553
[8]   GAP JUNCTION-MEDIATED INTERCELLULAR DIFFUSION OF CA-2+ IN CULTURED HUMAN CORPORAL SMOOTH-MUSCLE CELLS [J].
CHRIST, GJ ;
MORENO, AP ;
MELMAN, A ;
SPRAY, DC .
AMERICAN JOURNAL OF PHYSIOLOGY, 1992, 263 (02) :C373-C383
[9]   AUGMENTATION IN THE KINETIC CHARACTERISTICS OF PHENYLEPHRINE-INDUCED AND 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTIONS IN THE ISOLATED RAT AORTA FOLLOWING 8 WEEKS OF STZ-DIABETES [J].
CHRIST, GJ ;
VALCIC, M ;
GONDRE, MC .
LIFE SCIENCES, 1994, 55 (10) :807-814
[10]  
CHRIST GJ, 1993, J PHARMACOL EXP THER, V266, P1054