Background Stimulation of the heart β_3-adrenoceptor(AR)may result in a negative inotropic effect.Being up-regulated,β_3-AR plays a more important role in the regulation of cardiac function during heart failure.However,the effect of chronicblocking of β_3-AR on heart failure has not been fully elucidated.In this study,we used a selective β_3-AR antagonistSR59230A to treat a well defined heart failure rat model chronically,then evaluated its effect on cardiac function andinvestigated the mechanism.Methods Male Wistar rats were chosen randomly as controls(n=8).Isoproterenol induced heart failure rats wererandomly divided into ISO group(n=10)and SR group(n=10).The ISO group received intraperitoneal injection of 1 mlsaline 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 injectionand 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 enddiastolic dimension(LVEDd),left ventricular end systolic dimension(LVESd),ejection fraction(EF),fractionalshortening(FS)and the ratio of E wave to A wave(E/A),the mRNA and protein expression of β_3-AR and eNOS,andcGMP level in the heart.Results The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the controlgroup(P<0.01),but they were limited in the SR group(P<0.05 compared with the ISO group).CVF increased in the ISOgroup and the SR group(P<0.01),but it was significantly attenuated in the SR group(P<0.01).LVEDd,LVESd and E/Aratio were significantly increased in the ISO group compared with the control group(P<0.01),while EF and FS weresignificantly decreased(P<0.01).Compared with the ISO group,the SR group showed that LVEDd,LVESd and E/A ratiowere significantly decreased(P<0.01),whereas EF and FS were significantly increased(P<0.01).β_3-AR and eNOSmRNA and protein in the ISO group were significantly increased when compared with the control group(P<0.01).Theseincreases were all attenuated in the SR group compared with the ISO group(P<0.01).The level of cGMP in myocardialtissue was significantly increased in the ISO group compared with the control group(P<0.01),whereas SR59230Atreatment normalized this increment(P<0.01).Conclusions Chronic blocking of β_3-AR could ameliorate cardiac function in heart failure rats and its mechanisminvolves inhibition of the negative inotropic effect and attenuation of cardiac remodeling. Background Stimulation of the heart β_3-adrenoceptor (AR) may result in a negative inotropic effect. Beening up-regulated, β_3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic block of β_3 -AR on heart failure has not been fully elucidated. In this study, we used a selective β_3-AR antagonist SR59230A to treat a well-defined heart failure rat model chronically, then as its effect on cardiac function and investigated the mechanism. Methods Male Wistar rats were were randomly selected 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 mlsaline 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. 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 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 β_3-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 LVEDd, LVESd and E / Aratio were significantly increased in the ISO group compared with the control group (P <0.01), ISO group and the SR group (P <0.01), but it was significantly attenuated in the SR group , while EF and FS weresignificantly decreased (P <0.01) .Compared with the ISO group, the SR group showed that LVEDd, LVESd and E / A ratiowerered significantly (P <0.01), while EF and FS were significantly increased (P <0.01) .β_3-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P <0.01). The seincreases were all attenuated in the SR (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), while SR59230A treated normalized this increment (P <0.01) .Conclusions Chronic blocking of β_3-AR could ameliorate cardiac function in heart failure rats and its mechanisminvolves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.