Sodium Valproate, a Histone Deacetylase Inhibitor, but Not Captopril, Prevents Right Ventricular Hypertrophy in Rats

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Background: Although right ventricular hypertrophy (RVH) is an adaptive process to stresses such as outflow tract obstruction, uncorrected persistent RVH often results in failure of the right ventricle or even the left ventricle. Histone deacetylase (HDAC) inhibitors can effectively prevent or block left ventricular hypertrophy, so the present study compared the effects of sodium valproate, an HDAC inhibitor, with those of captopril, an angiotensin-converting enzyme inhibitor, on RVH. Methods and Results: RVH was induced in rats by pulmonary artery banding (PAB) or monocrotaline (MCT) injection, and then either sodium valproate or captopril was administered. PAB or MCT injection caused a marked increase in the size of RV after 2 weeks, which was documented by weighing it, by evaluating echocardiograms or electrocardiograms, or by examining cardiac hypertrophy-associated gene expression. Sodium valproate significantly reduced RVH induced by either PAB or MCT injection. Interestingly, however, captopril failed to do so. Conclusions: In the present study sodium valproate, but not captopril, was effective in blocking RVH induced by PAB or MCT injection, which suggests that HDAC inhibitors may be a novel therapy for RVH.