Effects of a novel histone deacetylase inhibitor, N-(2-aminophenyl) benzamide, on a reversible hypertrophy induced by isoproterenol in in situ rat hearts.
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| Abstract |
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.
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| Authors | Yutaka Kitagawa, Yamato Tamura, Juichiro Shimizu, Chikako Nakajima-Takenaka, Shigeki Taniguchi, Shinichi Uesato, Miyako Takaki |
| Journal | Journal of pharmacological sciences (J Pharmacol Sci) Vol. 104 Issue 2 Pg. 167-75 (Jun 2007) ISSN: 1347-8613 [Print] Japan |
| PMID | 17558183 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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