Effect of carvedilol on β_3-adrenoceptor expression in chronic heart failure

OBJECTIVE To investigate the expression of β3-adrenoceptor in rats with chronic heart failure,and to explore the effect of carvedilol on β3-adrenoceptor expression.METHODS Thirty-two male Wistar rats were divided into sham(n=10)and heart failure(n=24)groups.Heart failure group was treated with normal saline(heart failure control,n=6),low dose carvedilol(3 mg·kg-1·d-1,n=8)or high dose carvedilol(6 mg·kg-1·d-1,n=8)for three months.RESULTS The left ventricular end systolic pressure(LVESP)and the absolute values of maximal rate of rise and fall of left ventricular pressure(dp/dtmax)in the heart failure group were lower than in the Sham group(P0.01),whereas the left ventricular end diastolic pressure(LVEDP)was higher(P0.01).The LVESP and dp/dtmax in the high dose carvedilol group were higher than low dose carvedilol group whereas LVEDP was lower(P0.01).The left ventricular mass index(LVMI)in high dose carvedilol group was less than the low dose carvedilol and the heart failure control groups(P0.01).The level of β3-adrenoceptor expression in left ventricle in the study groups was significantly higher than the sham group(P0.01).β3-adrenoceptor expression in the high dose carvedilol group was lower than the heart failure control group and the low dose carvedilol group(P0.01).CONCLUSION β3-adrenoceptor expression is increased in the failing left ventricle in rats.High dose carvedilol is more effective than low dose in improving hemodynamics and in attenuating left ventricular remodeling after heart failure.High dose carvedilol,rather than low dose,diminishes β3-adrenoceptor expression in the failing left ventricle.