Curcumin prevents the development of hypertension-induced left ventricular hypertrophy in ratas

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.

  1. Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  2. Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
  3. Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto, Japan.
  4. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  5. 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.