The efficacy of
aliskiren, a
direct renin inhibitor, in
ventricular remodeling after
myocardial infarction (MI) compared with conventional renin-angiotensin system (RAS) inhibitors remains to be defined. This study was performed to examine the protective effects of
aliskiren and its addition to
valsartan, an
angiotensin-II receptor blocker, against
ventricular remodeling after MI. MI was induced in 8- to 12-week-old C57BL/6 mice by ligating the left anterior descending artery. At 3 days after MI, mice were divided into five groups and were treated with the following: (1)
phosphate-buffered saline (PBS); (2)
hydralazine (10 mg kg(-1) day(-1)); (3)
valsartan (8 mg kg(-1) day(-1)); (4)
aliskiren (25 mg kg(-1) day(-1)); and (5) combined
aliskiren (25 mg kg(-1) day(-1)) and
valsartan (8 mg kg(-1) day(-1)). With these doses of drugs, blood pressure-lowering effects compared with the PBS group were similar among the treated groups in
sham-operated mice. At 28 days after MI, echocardiographic, hemodynamic and histological assessments demonstrated that monotherapy with
valsartan or
aliskiren alone significantly and similarly ameliorated
ventricular remodeling after MI compared with the PBS and the
hydralazine groups. Combination
therapy of
valsartan and
aliskiren more greatly improved
ventricular remodeling after MI with enhancement of angiogenesis and greater attenuation of tissue oxidative stress and
inflammation. Our results indicate that
aliskiren can be an alternative to conventional RAS inhibitors in the treatment of post-MI patients. Moreover, the dual
therapy of
valsartan and
aliskiren may be more beneficial than either monotherapy. Further clinical trials will be warranted to sufficiently assess the safety and the efficacy of the use of
aliskiren in post-MI patients.