Curcumin prevents the development of hypertension-induced left ventricular hypertrophy in ratas
Yoichi Sunagawa1, Tatsuya Morimoto2, Teruhisa Kawamura1, Tomohide Takaya1, Hiromichi Wada1, Kazuhide Uemura2, Akira Shimatsu3, Takeshi Kimura4, Masatoshi Fujita5, Koji Hasegawa1.
- Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
- Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
- Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
- Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
American Heart Association Scientific Sessions 2009 (Orlando, USA), 2009/11/16 (Poster).
Abstract
Background: Hypertension causes left ventricular hypertrophy (LVH) with a preserved systolic function. While LVH might be a compensatory process, its presence of LVH is associated with an increased incidence of cardiovascular events and heart failure. Recently, we found that curcumin, a major curcumanoid isolated from Curcuma longa, inhibits the histone acetyltransferase (HAT) activity of p300 as well as the p300-induced acetylation of histones and a hypertrophy-responsive transcription factor,GATA-4, in cultured cardiomyocytes. Furthermore, curcumin prevents deterioration of the systolic function in rat heart failure models in vivo. However, whether curcumin prevents the development of hypertension-induced LHV at an early stage of hypertension is unclear.
Objective: To solve this problem, we have utilized a salt-sensitive Dahl rat (DS) model of hypertension.
Methods: We randomized 6-week-old DS (n = 19) and control salt-resistant Dahl rats (DR, n = 10) to a curcumin (Curc) or the vehicle (Veh) group. Then, these rats were given a high-salt diet and subjected to daily oral treatment with 50 mg/kg/day of curcumin or its vehicle for 5 weeks.
Results: There were no differences between Curc and Veh in any data examined before treatment (6 weeks of age). The high-salt diet induced a similar degree of hypertension in these two groups of DS compared with DR. At 11 weeks of age, transthoracic echocardiography in Veh showed that the LV wall thickness (DS: 2.0 mm, DR: 1.0 mm), LV mass (DS: 1.06 g/m2, DR: 0.64 g/m2), and LV fractional shortening (DS: 60%, DR: 50%) were significantly higher in DS compared with DR, and the LV systolic and diastolic dimensions were significantly smaller in DS than DR. Curcumin treatment significantly (p < 0.0001) decreased the LV wall thickness in DS (Curc: 1.4 mm, Veh: 2.0 mm) but not DR. Curcumin also significantly (p < 0.001) decreased the LV mass in DS (Curc: 0.76 g/m2, Veh: 1.06 g/m2), but not in DR. However, LV fractional shortening in DS was similar between the two groups (Curc: 57%, Veh: 60%).
Conclusions: The natural compound curcumin inhibits the development of hypertension-induced concentric LVH without affecting the systolic function. Thus, this compound might be applicable to patients with early-stages hypertensive heart diseases.