Effects of metoprolol on hemodynamics and expression of Bcl-2 and Bax proteins in heart failure rats

LIANG Qing; HUANG Min-jian; KUANG Su-hua; HUANG Wei-qing; GUO Min-jun; GUO Duan-qiang; YAN Ping; LIU Rong; LIN Jun-min; LIANG Zi-jing

Abstract：Objective To investigate the effects of metoprolol ( Meto) by different doses on hemodynamics and the myocardial expression of apoptosis related protein Bcl-2 and Bax in heart failure rats.Methods One hundred Spra-gue-Dawley rats were randomly divided into 5 groups ( n=20 ): sham group ( subjected to the same operation with the HF group but without ligation of abdominal aorta) , HF group ( subjected to the subtotal ligation of abdominal aorta) , Meto A group[subjected to the subtotal ligation of abdominal aorta and given with Meto 1.25 mg/(kg· d)], Meto B group [ subjected to the subtotal ligation of abdominal aorta and given with Meto 5 mg/( kg· d) ] , Meto C group [ subjected to the subtotal ligation of abdominal aorta and given with Meto 20 mg/( kg· d) ] .Different doses of Meto were given to the Meto treated groups 4 weeks after operation for 8 weeks.Invasive hemodynamic examination was performed before sacrifi-cing, and weighing heart wet weight (HW), lung wet weight (LW), heart weight index (heart weight/body weight, HW/BW) and the pulmonary weight index ( lung weight/body weight, LW/BW) were calculated.Anti-apoptotic gene Bcl-2 and pro-apoptotic gene Bax protein expression was assessed by western blotting.Results Compared with the HF group rats, the LVSP and +dp/dt max of the Meto treatment groups were significantly increased (P<0.01), with significantly reduced LVDP, LVEDP and -dp/dt max (P<0.01).Compared with Meto A and Meto B groups, LVSP of Meto C group was significantly reduced (P<0.01), and +dp/dt max of Meto C group was significantly lower than that of Meto B group ( P<0.01) .There was no significant difference in +dp/dt max between Meto C group and Meto A group, neither in LVDP, LVEDP nor -dp/dt max between Meto C and Meto B group.The HW/BW gradually decreased with increasing Meto dose (P<0.01).Compared with Meto A group, LW/BW of Meto B group was significantly reduced (P<0.01), but LW/BW of Meto C group was significantly increased while compared with Meto B group (P<0.01).The myocardial Bcl-2/Bax ratio in HF group was significantly reduced while compared with sham group ( P<0.05 ) , and with the in-crease in Meto treatment groups, Bcl-2/Bax ratio of Meto treatment groups were gradually increased, which was flipped over in Meto B group.Conclusion Medium-dose of Meto in HF rats can obtain anatomic pathological and anti-apopto-sis benefit and ensures maximum hemodynamic benefit at the same time, but large-dose Meto treatment may inhibit fur-ther improvement of the heart function.