Skip Navigation

Cardiovascular Research 2002 54(1):85-94; doi:10.1016/S0008-6363(01)00553-3
© 2002 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 Fraccarollo, D.
Right arrow Articles by Ertl, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fraccarollo, D.
Right arrow Articles by Ertl, G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2002, European Society of Cardiology

Cardioprotection by long-term ETA receptor blockade and ACE inhibition in rats with congestive heart failure: mono- versus combination therapy

Daniela Fraccarollo1, Johann Bauersachs1, Markus Kellner, Paolo Galuppo and Georg Ertl*

Medizinische Klinik, Julius-Maximilians-Universität Würzburg, Josef-Schneider-Str. 2, D-97080 Würzburg, Germany

g.ertl{at}medizin.uni-wuerzburg.de

* Corresponding author. Tel.: +49-931-201-5301; fax: +49-931-201-5302

Objectives: We investigated the effects of long-term endothelin A (ETA) receptor blockade and ACE inhibition, either alone or in combination, on the hemodynamics, neurohormonal activation and cardiac remodeling in rats with congestive heart failure (CHF) after extensive myocardial infarction (MI). Methods: Rats were treated with placebo, the ETA antagonist LU135252 (30 mg/kg/d), the ACE inhibitor trandolapril (0.3 mg/kg/d), or a combination of both for 11 weeks, starting 7 days after MI. Results: Despite comparable effects on left ventricular (LV) systolic pressure among all drug treatments, only combined ETA and ACE inhibition significantly reduced LV end-diastolic pressure (P<0.01), improved LV dP/dtmax (P<0.01) and normalized sympathetic activation (P<0.05) in rats with CHF. The combination therapy was more effective in reducing type I and III collagen mRNA levels, MMP-2 zymographic activity and collagen accumulation in the surviving LV myocardium. Moreover, the increases in cardiac β-myosin heavy chain and skeletal {alpha}-actin mRNAs, markers of hypertrophy or failure, were attenuated to a greater degree by the combination therapy than monotherapy, whereas right ventricular hypertrophy and ANF mRNA upregulation were significantly (P<0.01) prevented only by combined ETA and ACE inhibition. Conclusion: Long-term combined ETA receptor and ACE inhibition improved cardiac failure after extensive MI more effectively than monotherapy. We show additive effects on LV fibrosis and fetal gene expression. ETA receptor antagonists could be a therapeutical option in CHF in addition to an ACE inhibitor.

KEYWORDS Infarction; Heart failure; Endothelins; Angiotensin; Fibrosis

1 Both authors contributed equally to this work.


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
 Circ Heart FailHome page
A. Garnier, J. Zoll, D. Fortin, B. N'Guessan, F. Lefebvre, B. Geny, B. Mettauer, V. Veksler, and R. Ventura-Clapier
Control by Circulating Factors of Mitochondrial Function and Transcription Cascade in Heart Failure: A Role for Endothelin-1 and Angiotensin II
Circ Heart Fail, July 1, 2009; 2(4): 342 - 350.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
T. Thum, D. Fraccarollo, M. Schultheiss, S. Froese, P. Galuppo, J. D. Widder, D. Tsikas, G. Ertl, and J. Bauersachs
Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes
Diabetes, March 1, 2007; 56(3): 666 - 674.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs
Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells
Cardiovasc Res, April 1, 2006; 70(1): 50 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. Vanhoutte, M. Schellings, Y. Pinto, and S. Heymans
Relevance of matrix metalloproteinases and their inhibitors after myocardial infarction: A temporal and spatial window
Cardiovasc Res, February 15, 2006; 69(3): 604 - 613.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. Fernandes, J.-C. Amirault, G. Lande, J.-M. Nguyen, V. Forest, O. Bignolais, G. Lamirault, D. Heudes, J.-L. Orsonneau, M.-F. Heymann, et al.
Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias
Cardiovasc Res, February 1, 2006; 69(2): 348 - 358.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. Fraccarollo, P. Galuppo, I. Schmidt, G. Ertl, and J. Bauersachs
Additive amelioration of left ventricular remodeling and molecular alterations by combined aldosterone and angiotensin receptor blockade after myocardial infarction
Cardiovasc Res, July 1, 2005; 67(1): 97 - 105.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
N. Emoto, S. B. Raharjo, D. Isaka, S. Masuda, S. Adiarto, A. Y. Jeng, and M. Yokoyama
Dual ECE/NEP Inhibition on Cardiac and Neurohumoral Function During the Transition From Hypertrophy to Heart Failure in Rats
Hypertension, June 1, 2005; 45(6): 1145 - 1152.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. Ertl and S. Frantz
Healing after myocardial infarction
Cardiovasc Res, April 1, 2005; 66(1): 22 - 32.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. B. Murray, J. D. Gardner, G. L. Brower, and J. S. Janicki
Endothelin-1 mediates cardiac mast cell degranulation, matrix metalloproteinase activation, and myocardial remodeling in rats
Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2295 - H2299.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
Y. Nakano, S. Niida, K. Dote, S. Takenaka, H. Hirao, F. Miura, M. Ishida, T. Shingu, T. Sueda, M. Yoshizumi, et al.
Matrix metalloproteinase-9 contributes to human atrial remodeling during atrial fibrillation
J. Am. Coll. Cardiol., March 3, 2004; 43(5): 818 - 825.
[Abstract] [Full Text] [PDF]

Home page
 Eur J Heart FailHome page
A. Schafer, D. Fraccarollo, P. Tas, I. Schmidt, G. Ertl, and J. Bauersachs
Endothelial dysfunction in congestive heart failure: ACE inhibition vs. angiotensin II antagonism
Eur J Heart Fail, March 1, 2004; 6(2): 151 - 159.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
D. Fraccarollo, P. Galuppo, S. Hildemann, M. Christ, G. Ertl, and J. Bauersachs
Additive improvement of left ventricular remodeling and neurohormonal activation by aldosterone receptor blockade with eplerenone and ACE inhibition in rats with myocardial infarction
J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1666 - 1673.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
G. P. Rossi, C. Ganzaroli, M. Cesari, A. Maresca, M. Plebani, G. G. Nussdorfer, and A. C. Pessina
Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension
Cardiovasc Res, January 1, 2003; 57(1): 277 - 283.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. Fraccarollo, P. Galuppo, J. Bauersachs, and G. Ertl
Collagen accumulation after myocardial infarction: effects of ETA receptor blockade and implications for early remodeling: Presented in part at the 72nd Scientific Session of the American Heart Association, Atlanta, GA, USA, November 7-10, 1999, and published in abstract form (Circulation 1999;100(Suppl. 1):562)
Cardiovasc Res, June 1, 2002; 54(3): 559 - 567.
[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.