Aliskiren Improves Left Ventricular Dysfunction and Reduces Cardiac Dilation in Syrian Cardiomyopathic Hamsters

Objective: Chronic activation of the renin-angiotensin-aldosterone system is a major contributing factor to the pathogenesis and progression of cardiovascular and renal diseases. Methods: To evaluate the role of renin-angiotensin-aldosterone system blockade with aliskiren, a direct renin inhibitor, in the development and progression of dilated cardiomyopathy in the Syrian cardiomyopathic hamster (SCH) model, we treated 1-month-old SCH with aliskiren (10 mg . kg(-1).d(-1)) over a 4-month period. For comparative purposes, we also evaluated the effects of the angiotensin receptor blocker valsartan (10 mg . kg(-1).d(-1)) and the combination of both drugs. Age-matched golden hamsters were used as controls. Left ventricular end-diastolic volume and end-systolic volume, ejection fraction, and diastolic function were determined by echocardiography. Systolic blood pressure (SBP) was also measured in the left femoral artery by sphygmomanometry. Results: Results indicate that at 2 months of age, SBP is higher in SCH than in controls, and administration for 1 month of aliskiren, valsartan, or the combination of these drugs normalized SBP in SCH to a similar extent. In 5-month-old SCH, aliskiren improved ejection fraction (from 48.6% +/- 5.8% to 69.4% +/- 3.2%, n = 5, P < 0.05), left ventricular end-systolic volume (from 0.28 +/- 0.06 to 0.10 +/- 0.01 mL/100 g body weight), left ventricular end-diastolic volume (from 0.61 +/- 0.05 to 0.34 +/- 0.02 mL/100 g body weight), and normalized diastolic function (E: A ratio increases from 0.93 +/- 0.13 to 1.70 +/- 0.03, n = 5, P < 0.05). Similar results were observed with valsartan or the combination of aliskiren and valsartan. Conclusions: Our results indicate that in this animal model, aliskiren is as effective as valsartan, or the combination of both drugs, in improving diastolic function and in preventing the development of dilated cardiomyopathy. These findings suggest that aliskiren may be used as a monotherapy in heart failure management. Clinical studies, however, are needed to assess the effectiveness of this drug in patients with heart failure.