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 controI 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).LVESd,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 showed that LVEDd,LVESd and E/A ratio were significantly decreased(P<0.01),whereas EF and FS were significantly increased(P<0.01).β3-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group(P<0.01).These increases were all attenuated in the SR group compared with the ISO group(P<0.01).The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group(P<0.01),whereas SR59230A treatment normalized this increment(P<0.01).Conclusions Chronic blocking of β3-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.