Chronic blocking of β_3-adrenoceptor ameliorates cardiac function in rat model of heart failure

作     者：GAN Run-tao LI Wei-min XIU Chun-hong SHEN Jing-xia WANG Xu WU Shuang KONG Yi-hui 

作者机构：Department of Cardiology First Clinical Hospital Harbin Medical University Harbin 150001 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2007年第120卷第24期

页      面：2250-2255页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学] 

基　　金：This study was supported by grants from the Science and Technology Fund of Heilongjiang Education Bureau(No.11511228) the Innovation Fund of Harbin Medical University for Graduate Students(No.200401060) 

主　　题：adrenoceptor cardiac function antagonist heart failure rats 

摘      要：Background Stimulation of the heart β3-adrenoceptor （AR） may result in a negative inotropic effect. Being up-regulated, β3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of β3-AR on heart failure has not been fully elucidated. In this study, we used a selective β3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism. Methods Male Wistar rats were chosen randomly as controls （n=-8）. Isoproterenol induced heart failure rats were randomly divided into ISO group （n=-10） and SR group （n=10）. The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes： the ratio of heart weight to body weight （HW/BW） and the ratio of left ventricular weight to body weight （LVW/BW）, collagen volume fraction （CVF）, left ventricular end diastolic dimension （LVEDd）, left ventricular end systolic dimension （LVESd）, ejection fraction （EF）, fractional shortening （FS） and the ratio of E wave to A wave （E/A）, the mRNA and protein expression of β3-AR and eNOS, and cGMP level in the heart. Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group （P〈0.01）, but they were limited in the SR group （P〈0.05 compared with the ISO group）. CVF increased in the ISO group and the SR group （P〈0.01）, but it was significantly attenuated in the SR group （P〈0.01）. LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group （P〈0.01）, while EF and FS were significantly decreased （P〈0.01）. Compared with the ISO group, the SR group showe