Skip Navigation

Cardiovascular Research 1999 41(1):100-108; doi:10.1016/S0008-6363(98)00227-2
© 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 Richer, C.
Right arrow Articles by Giudicelli, J.-F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Richer, C.
Right arrow Articles by Giudicelli, J.-F.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1999, European Society of Cardiology

Effects of long-term angiotensin II AT1 receptor blockade on survival, hemodynamics and cardiac remodeling in chronic heart failure in rats1

Christine Richera, Paul Fornesa, Catherine Cazaubonb, Valérie Domerguea, Dino Nisatob and Jean-François Giudicellia,*

aDépartement de Pharmacologie, Faculté de Médecine Paris-Sud, 63 rue Gabriel Péri, 94276 Le Kremlin-Bicêtre Cedex, France
bDépartement de Recherche Cardiovasculaire, Sanofi Recherche, 371, rue du Pr. J. Blayac, 34184 Montpellier Cedex 04, France

* Corresponding author. Tel.: +33-1-4959-6701; fax: +33-1-4960-0031.

Objective: The beneficial effect of chronic angiotensin I converting enzyme (ACE) inhibition on survival has for long been established in the rat post-infarction model of chronic heart failure (CHF) and has subsequently been confirmed in humans. This study investigates in rats whether chronic angiotensin II AT1 receptor blockade shares with ACE inhibition the same beneficial effect. Methods: Rats were subjected to coronary artery ligation and, from 7 days later, orally treated for 7.5 months with placebo or irbesartan (5 or 50 mg/kg/day). Results: Irbesartan dose-dependently increased survival (placebo: 27%, low dose: 52%, high dose: 82%, sham-ligated: 100%; high dose vs placebo: P<0.001 and vs low dose: P<0.05; low dose vs placebo: P=0.11). Irbesartan also dose-dependently decreased urinary cyclic GMP excretion throughout the study. At 7.5 months, it dose-dependently decreased left ventricular (LV) end diastolic pressure, normalized LV pressure maximal rate of rise (dP/dt) and cardiac index values and improved LV and right ventricular regional blood flows (radioactive microspheres) and resistances. At 7.5 months, irbesartan markedly decreased myocardial hypertrophy but had almost no effect on LV dilatation and subendocardial fibrosis. Conclusions: Long-term angiotensin II AT1 receptor blockade with irbesartan strongly and dose-dependently increases survival in the rat model of coronary ligation-induced CHF. This effect is due to the combination of the beneficial effects that the drug exerts on systemic and coronary hemodynamics, on cardiac pump function and vs cardiac hypertrophy development. Long-term AT1 receptor blockade might thus prove useful and prolong survival in human CHF.

KEYWORDS Experimental heart failure; Survival; Angiotensin II AT1 receptor blockade; Hemodynamics; Cardiac remodeling; Rat


1 See pages 14–15.


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
Am. J. Physiol. Heart Circ. Physiol.Home page
G. E. Gonzalez, I. M. Seropian, M. L. Krieger, J. Palleiro, M. A. Lopez Verrilli, M. M. Gironacci, S. Cavallero, L. Wilensky, V. H. Tomasi, R. J. Gelpi, et al.
Effect of early versus late AT1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H375 - H386.
[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 CARDIOVASC PHARMACOL THERHome page
B. I. Jugdutt, Yi Xu, M. Balghith, R. Moudgil, and V. Menon
Cardioprotection Induced by AT1R Blockade After Reperfused Myocardial Infarction: Association With Regional Increase in AT2R, IP3R and PKC{varepsilon} Proteins and cGMP
Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(4): 301 - 311.
[Abstract] [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.