Tomoko Tokioka-Akagi1,*, Akira Fujimori2, Masayuki Shibasaki2, Osamu Inagaki2 and Isao Yanagisawa2
1Clinical Development Coordination Department, Yamanouchi Pharmaceutical Co., Ltd., 3-17-1 Hasune, Itabashi-ku, Tokyo 174-8612, Japan
2Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
*Corresponding author. FAX: +81-3-5916-2625, E-mail: firstname.lastname@example.org
Abstract: We evaluated the effects of chronic oral administration of an angiotensin II type 1 (AT1)-receptor antagonist YM358 and an angiotensin converting enzyme inhibitor enalapril on hemodynamics and cardiac hypertrophy in rats with volume overload-induced heart failure. We assessed changes of cardiac hemodynamics and cardiac hypertrophy at 2 and 4 weeks after administration of YM358 (3, 30 mg/kg per day) or enalapril (30 mg/kg per day) in abdominal aortocaval shunt rats. YM358 (30 mg/kg) attenuated increases of left ventricle (LV)/body weight (BW), left atrium (LA)/BW, right ventricle (RV)/BW and heart/BW ratios, but did not affect cardiac hemodynamics in shunt rats. Enalapril also reduced the increased LV/BW and heart/BW ratios together with significant reductions of systolic blood pressure, left ventricular systolic pressure and the first derivative of left ventricular pressure. These data suggest that the effects on attenuation of the development of cardiac hypertrophy are not different for YM358 and enalapril, although the effects on cardiac hemodynamics are different for the same dosages. The attenuating action of YM358 on cardiac hypertrophy was independent of the action on hemodynamics and indicated the direct action of the AT1 receptor on the heart.
Keywords: Cardiac hypertrophy, Heart failure, Aortocaval shunt, Angiotensin II type 1-receptor antagonist, Angiotensin-converting enzyme inhibitor
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