Sodium valproate, a histone deacetylase inhibitor, but not captopril, prevents right ventricular hypertrophy in rats.
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.


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.
Cho
Young Kuk
YK
Department of Pediatrics, Chonnam National University Hospital, Gwangju, South Korea.
Eom
Gwang Hyeon
GH
Kee
Hae Jin
HJ
Kim
Hyung-Seok
HS
Choi
Woo-Yeon
WY
Nam
Kwang-Il
KI
Ma
Jae Sook
JS
Kook
Hyun
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000627:therapeutic use*; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors / Q000627:therapeutic use*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D008026:Ligation; D008297:Male; D016686:Monocrotaline / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000627:therapeutic use*
D000806:Angiotensin-Converting Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid; D016686:Monocrotaline; D002216:Captopril