Cardioprotection by long-term ETA receptor blockade and ACE inhibition in rats with congestive heart failure: mono- versus combination therapy
Open Access
- 1 April 2002
- journal article
- research article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 54 (1) , 85-94
- https://doi.org/10.1016/s0008-6363(01)00553-3
Abstract
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 (PP/dtmax (PPPA 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
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