The effect of the renin–angiotensin–aldosterone system inhibition on myocardial function in early and late phases of dilated cardiomyopathy in Tgaq*44 mice

Background: The renin–angiotensin–aldosterone system (RAAS) determines progression of heart failure (HF) in humans, and RAAS inhibition is a major therapeutic strategy in HF. Aim: To assess the effect of angiotensin-converting enzyme inhibitor (ACE-I) and aldosterone receptor antagonist (ARA) therapy on the development of HF at its early and late stage in a murine model of dilated cardiomyopathy (Tgaq*44 mice). Methods: Tgaq*44 mice at the early or advanced stage of HF received combined therapy including ACE-I (perindopril 2 mg/kg) and ARA (canrenone 20 mg/kg). Cardiac function was assessed by magnetic resonance imaging before and after 2 months of treatment. Results: Combined therapy with perindopril and canrenone resulted in preserved systolic function at the early stage and reduced chamber dilatation at the advanced stage of HF in Tgaq*44 mice. Conclusions: Activation of the RAAS is involved in progression of HF in Tgaq*44 mice with dilated cardiomyopathy. Therapeutic efficacy of ACE-I and ARA to inhibit systolic dysfunction and cardiac chamber dilation depends on the stage of HF development.