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

Kardiol Pol. 2013;71(7):730-7. doi: 10.5603/KP.2013.0161.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Canrenone / pharmacology
  • Cardiovascular Agents / pharmacology*
  • Dobutamine / pharmacology
  • Heart Failure / drug therapy*
  • Heart Failure / prevention & control
  • Mice
  • Mice, Transgenic
  • Models, Animal
  • Perindopril / pharmacology
  • Renin-Angiotensin System / drug effects*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Cardiovascular Agents
  • Dobutamine
  • Canrenone
  • Perindopril