Long-Term Survival and Hemodynamics After Endothelin-A Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition in Rats With Chronic Heart Failure
Open Access
- 27 August 2002
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 106 (9), 1159-1164
- https://doi.org/10.1161/01.cir.0000027138.07524.38
Abstract
Background— In patients with congestive heart failure (CHF) receiving ACE inhibitors, acute administration of selective endothelin (ET) antagonists additionally improves systemic and cardiac hemodynamics. We investigated, in a rat model of CHF, whether such acute synergistic effects are sustained and accompanied, in the long term, by an additional limitation of left ventricular remodeling or an increase in survival. Methods and Results— Rats were subjected to coronary artery ligation and treated for 3 or 9 months with vehicle or with the ACE inhibitor trandolapril (Tr) (0.3 mg/kg −1 per day −1 ), the ET A antagonist LU 135252 (LU, 30 mg/kg −1 per day −1 ), or their combination starting 7 days after ligation. After 3 months, the combination decreased LV systolic- and end-diastolic pressures (−32% and −80%, respectively) more markedly than Tr (−21% and −61%, respectively) or LU alone (−14% and −48%, respectively). Echocardiographic studies revealed that all treatments limited LV dilatation and increased LV fractional shortening and cardiac index. All treatments equally reduced left ventricular collagen density, whereas only Tr or the combination reduced LV weight. Finally, although LU did not modify long-term survival, Tr and the combination of Tr with LU induced a similar improvement of survival. Conclusions— In this rat model, long-term combined administration of an ET A antagonist and an ACE inhibitor induces additional effects in terms of systemic and cardiac hemodynamics; however, this is not associated with an additional increase in long-term survival.Keywords
This publication has 14 references indexed in Scilit:
- Hemodynamic effects of bosentan in patients with chronic heart failure.Heart Failure Reviews, 2001
- Endothelin Antagonism in Experimental Ischemic Heart Failure: Hemodynamic, Structural and Neurohumoral EffectsHeart Failure Reviews, 2001
- Acute hemodynamic and neurohumoral effects of selective ETA receptor blockade in patients with congestive heart failureJournal of the American College of Cardiology, 2000
- Long-term survival in severe heart failure in patients treated with enalapril; ten year follow-up of CONSENSUS IPublished by Oxford University Press (OUP) ,1999
- Selective ETA receptor blockade prevents left ventricular remodeling and deterioration of cardiac function in experimental heart failureCardiovascular Research, 1998
- Comparison of the acute effects of a selective endothelin ETA and a mixed ETA/ETB receptor antagonist in heart failureCardiovascular Research, 1998
- Inhibition of myocardial endothelin pathway improves long-term survival in heart failureNature, 1996
- Purinergic regulation of anion secretion by cystic fibrosis pancreatic duct cellsAmerican Journal of Physiology-Cell Physiology, 1996
- Effect of Captopril on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial InfarctionNew England Journal of Medicine, 1992
- Increased levels of messenger ribonucleic acid for apolipoprotein E in the spleen of probucol-treated rabbitsThe American Journal of Cardiology, 1988