Effects of a novel histone deacetylase inhibitor, N-(2-aminophenyl) benzamide, on a reversible hypertrophy induced by isoproterenol in in situ rat hearts.
The aim of the present study was performed to determine whether a novel histone deacetylase (HDAC) inhibitor, N-(2-aminophenyl)-4-{[benzyl(2-hydroxyethyl)amino]methyl} benzamide (K-183), prevents a reversible cardiac hypertrophy induced by isoproterenol and improves left ventricular (LV) dysfunction in rats. Either isoproterenol or vehicle was infused for 3 days by osmotic minipump. One hour prior to the implantation of isoproterenol, K-183 or trichostatin A (TSA) was injected twice a day for 3 days. We recorded continuous LV pressure-volume (P-V) loops of in situ hearts one hour after removal of the osmotic minipump. LV work capability (systolic P-V area at midrange LV volume: PVA(mLVV)) and hemodynamics were evaluated. K-183 per se induced neither cardiac hypertrophy nor collagen production. Although K-183 did not prevent the hypertrophy, where PVA(mLVV) remained decreased, K-183, differently from TSA, significantly attenuated the decrease of cardiac output and the increase of effective arterial elastance in the hypertrophied heart. These results indicate that the novel HDAC inhibitor K-183 has some beneficial effects on hemodynamics, although K-183 has no effects of anti-hypertrophic modalities.
Kitagawa
Yutaka
Y
Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Tamura
Yamato
Y
Shimizu
Juichiro
J
Nakajima-Takenaka
Chikako
C
Taniguchi
Shigeki
S
Uesato
Shinichi
S
Takaki
Miyako
M
D000704:Analysis of Variance; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000517:prevention & control*; D003094:Collagen / Q000096:biosynthesis / Q000187:drug effects; D004195:Disease Models, Animal; D056572:Histone Deacetylase Inhibitors; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D007545:Isoproterenol; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013318:Stroke Volume; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*; D017725:Ventricular Pressure
D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; C522127:N-(2-aminophenyl)-4-((benzyl(2-hydroxyethyl)amino)methyl) benzamide; D003094:Collagen; D007545:Isoproterenol