[Effect of beta3-adrenoceptor antagonist on the cardiac function and expression of endothelial nitric oxide synthase in a rat model of heart failure].

ABSTRACT

OBJECTIVE: To investigate the effect of beta(3)-adrenoceptor (beta(3)-AR) antagonist (SR59230A) on the cardiac function and left ventricular remodeling in a rat model of heart failure induced by isoproterenol (ISO), and to probe into its mechanism. METHODS: Eight rats were randomly selected to serve as controls from 85 male adult Wistar rats. After a heart failure model was reproduced, twenty remain rats were randomly divided into ISO group (n = 10) and SR59230A group (SR group, n = 10). ISO group received intraperitoneal injection of 1 ml saline twice a day; SR group received intraperitoneal injection of 85 nmol SR59230A in 1 ml saline twice a day; control group received no treatment. The parameters determined included echocardiogram, the expression of nitric oxide synthase (eNOS) of left ventricle by the technique of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, cyclic guanosine monophosphate (cGMP) level by enzyme linked immunosorbent assay (ELISA), the ratio of left ventricular weight and body weight (LVW/BW), and the ratio of lung weight and body weight (PW/BW). RESULTS: Compared with control group, the left ventricular end systolic pressure (LVESP), the maximum and minimum first derivative of left ventricular pressure (+/-dp/dtmax) were significantly decreased (all P<0.01), while heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) were significantly increased (both P<0.01) in ISO group. Compared with ISO group, LVESP, +/-dp/dtmax were markedly higher (P<0.05 or P<0.01) respectively, whereas HR and LVEDP were markedly lower (P<0.05 and P<0.01) in SR group, and there was no difference in HR between SR group and control group (P>0.05), while LVEDP was higher in RS group than control group (P<0.01). The levels of eNOS mRNA, protein and cGMP were significantly lower in SR group compared with ISO group (all P<0.01). In addition, when compared with ISO group, LVW/BW ratio and PW/BW ratio in SR group were also decreased (both P<0.05). CONCLUSION: beta(3)-AR antagonist SR59230A can block the beta(3)-AR-NOS-cGMP pathway and improve cardiac function in heart failure in rat when if is administered for a long term. SR59230A can also improve left ventricular remodeling in a certain degree.