Skip Navigation

Cardiovascular Research 1999 43(2):445-456; doi:10.1016/S0008-6363(99)00097-8
© 1999 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Dashwood, M. R
Right arrow Articles by Münter, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dashwood, M. R
Right arrow Articles by Münter, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1999, European Society of Cardiology

Altered endothelin-1 binding following balloon angioplasty of pig coronary arteries: effect of the ETA receptor antagonist, LU 135252

Michael R Dashwooda, Peter Noertersheuserc, Michael Kirchengastb and Klaus Münterb,*

aDepartment of Chemical Pathology and Human Metabolism, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK
bDepartment of Cardiovascular Pharmacology, Knoll AG, P.O. Box 210805, D-67008 Ludwigshafen, Germany
cDepartment of Biostatistics and Data Management, Knoll AG, P.O. Box 210805, D-67008 Ludwigshafen, Germany

* Corresponding author. Tel.: +49-621-5892559; fax: +49-621-5891405 klaus.muenter{at}knoll-ag.de

Objective: Since raised levels of endothelin-1 (ET-1) have been detected in the human coronary sinus following percutaneous transluminal angioplasty (PTCA) we investigated the role of ET-1 in the etiology of vascular restenosis. Methods: Balloon angioplasty of coronary arteries was performed in pigs and the animals were treated with placebo or the endothelin (ETA) receptor antagonist LU 135252 (30 mg/kg/day). After 4 weeks vascular stenosis and the distribution of endothelin and its receptors was evaluated. Results: The pronounced neointima formation in the control group (neointima:media ratio=0.87±0.36) was significantly reduced by LU 135252 (0.43±0.30, P<0.001). Angioplasty caused a significant increase in medial ETA (approximately 275%, P<0.026) and ETB (approximately 250%, P<0.001) binding to injured, compared with non-injured segments, an effect that was also reduced by LU 135252 (ETA=11.5% increase; ETB=14% increase). The neointima of control animals exhibited ET-1 like immunoreactivity as well as ETA and ETB binding sites. Conclusion: These data indicate that endothelin is locally-released from endothelial and vascular smooth muscle cells following angioplasty which binds to ETA and ETB receptor sites in the neointima and media. Since administration of the ETA antagonist LU 135252 markedly reduces neointima formation and medial ET binding, we conclude that vascular smooth muscle cell proliferation and subsequent neointima formation is mediated predominantly via ETA receptors. These data underscore the therapeutic potential of ETA antagonists in reducing the degree of restenosis following vascular injury.

KEYWORDS Experimental; Vasculature; Pharmacology angioplasty; Coronary arteries; Endothelin receptors; Restenosis; Histology


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
D. W. Anggrahini, N. Emoto, K. Nakayama, B. Widyantoro, S. Adiarto, N. Iwasa, H. Nonaka, Y. Rikitake, Y. Y. Kisanuki, M. Yanagisawa, et al.
Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation
Cardiovasc Res, April 1, 2009; 82(1): 143 - 151.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
S. Wan, A. P. C. Yim, J. L. Johnson, N. Shukla, G. D. Angelini, F. C. T. Smith, M. R. Dashwood, and J. Y. Jeremy
The endothelin 1A receptor antagonist BSF 302146 is a potent inhibitor of neointimal and medial thickening in porcine saphenous vein-carotid artery interposition grafts
J. Thorac. Cardiovasc. Surg., May 1, 2004; 127(5): 1317 - 1322.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Forte, S. Esposito, M. De Feo, U. Galderisi, C. Quarto, F. Esposito, A. Renzulli, L. Berrino, M. Cipollaro, L. Agozzino, et al.
Stenosis progression after surgical injury in Milan hypertensive rat carotid arteries
Cardiovasc Res, December 1, 2003; 60(3): 654 - 663.
[Abstract] [Full Text] [PDF]

Home page
 ANGIOLOGYHome page
M. R. Dashwood and J. C. S. Tsui
Endothelins and the 'French Paradox': Are Detrimental Effects of Red Wine Also Associated with an Action on Endothelin Synthesis?
Angiology, November 1, 2002; 53(6): 749 - 751.
[PDF]

Home page
 Cardiovasc ResHome page
A. W Barolet, S. Babaei, R. Robinson, P. Picard, W. Tsui, N. Nili, F. Mohamed, O. Ornatsky, J. D Sparkes, D. J Stewart, et al.
Administration of exogenous endothelin-1 following vascular balloon injury: early and late effects on intimal hyperplasia
Cardiovasc Res, December 1, 2001; 52(3): 468 - 476.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
W. R. Huckle, M. D. Drag, W. R. Acker, M. Powers, R. C. McFall, D. J. Holder, T. F. Walsh, R. S. Schwartz, W. J. Greenlee, and R. G. Johnson Jr
Effects of L-749,329, an ETA/ETB Endothelin Receptor Antagonist, in a Porcine Coronary Artery Injury Model of Vascular Restenosis
Circulation, April 10, 2001; 103(14): 1899 - 1905.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.