Key result
Combined treatment with an ACE inhibitor and an AT1 antagonist did not improve cardiac function more than either agent alone in mice with heart failure.
Why the study?
Does combined treatment with an ACE inhibitor and an AT1 antagonist improve cardiac function more than either agent alone in a mouse model of heart failure?
Does combined treatment with an ACE inhibitor and an AT1 antagonist improve cardiac function more than either agent alone in a mouse model of heart failure?
In a mouse model of heart failure, combining an ACE inhibitor and an AT1 antagonist provides no additional cardioprotective benefit over either agent alone.
Answers are grounded in this paper and cite their sources.
Does not support combined ACEi/ARB use in HF; leaves open potential benefits in human disease.
We tested the hypothesis that a combination of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II type 1 receptor antagonist (AT1-ant) may have an additive cardioprotective effect in mice with heart failure (HF), because these two agents could have other mechanisms of action besides interrupting the renin-angiotensin system. ACEi prevent degradation of bradykinin. During treatment with AT1-ant, increased angiotensin II could activate AT2 receptors, with an antitrophic effect. To test this hypothesis, we used a mouse model of HF induced by myocardial infarction. Seven days after surgery, mice were divided into six groups and treated for 23 weeks: (a) sham ligation; (b) HF-vehicle; (c) HF-ACEi; (d) HF-AT1-ant; (e) HF-ACEi + AT1-ant (half dose of each); and (f) HF-ACEi + AT1-ant (full dose of each). Cardiac function was evaluated in conscious mice during the treatment period. The HF-vehicle group showed significantly decreased left ventricular (LV) ejection fraction (EF), shortening fraction (SF), and cardiac output (CO) and increased LV dimensions, interstitial collagen, and myocyte cross-sectional area (MCSA) compared with controls. Treatment with ACEi or AT1-ant significantly increased EF, SF, and CO and decreased LV dimensions and MCSA in mice with HF. However, a combination of these drugs did not improve cardiac function more than ACEi or AT1-ant alone. We concluded that ACEi and AT1-ant have similar cardioprotective effects and may reach maximal effect when given individually; thus no further improvement can be achieved with combined therapy in mice with HF.
No takes yet. Share an insight, caveat, or question.
Cavasin et al. (2000) studied Heart failure. ACE inhibitor and AT1 antagonist combination vs. Vehicle, ACE inhibitor alone, or AT1 antagonist alone was evaluated on Cardiac function (left ventricular ejection fraction, shortening fraction, and cardiac output) and LV dimensions. Combined treatment with an ACE inhibitor and an AT1 antagonist did not improve cardiac function more than either agent alone in mice with heart failure.
Synapse has enriched 10 related papers. Consider them for comparative context: