Effects of a novel histone deacetylase inhibitor, N-(2-aminophenyl) benzamide, on a reversible hypertrophy induced by isoproterenol in in situ rat hearts

J Pharmacol Sci. 2007 Jun;104(2):167-75. doi: 10.1254/jphs.fp0070091. Epub 2007 Jun 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Benzamides / pharmacology*
  • Cardiac Catheterization
  • Cardiac Output / drug effects
  • Cardiomegaly / chemically induced
  • Cardiomegaly / prevention & control*
  • Collagen / biosynthesis
  • Collagen / drug effects
  • Disease Models, Animal
  • Histone Deacetylase Inhibitors*
  • Hypertrophy, Left Ventricular / drug therapy*
  • Isoproterenol
  • Male
  • Rats
  • Rats, Wistar
  • Stroke Volume
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Pressure

Substances

  • Benzamides
  • Histone Deacetylase Inhibitors
  • N-(2-aminophenyl)-4-((benzyl(2-hydroxyethyl)amino)methyl) benzamide
  • Collagen
  • Isoproterenol