Biological effects of the autoantibody against β_3-adrenoceptor from the sera of rats with heart failure

AIM: To investigate the relation between myocardial remodeling and the genesis of serum anti-β_3-adrenoceptor autoantibody,an animal model of heart failure(HF) was established and the biological effects of the autoantibody were observed.METHODS:(1) Healthy male Wistar rats were subjected to HF by constricting the abdominal aorta.(2) The anti-β_3-adrenoceptor autoantibody in the sera of HF rats was detected by ELISA with the synthetic peptide of the second extracellular loop of the β_3-adrenoceptor used as the antigen.(3) IgG in the positive sera from HF rats was prepared using a MabTrap Kit(Amersham).(4) The effects of the autoantibody on the contractile response of adult(isolated) cardiomyocytes and on the beating rate of cultured neonatal rat cardiomyocytes were observed.RESULTS:(1) The positive rate of anti-β_3-adrenoceptor autoantibody of rats increased from 21.05% of pretreatment to 78.95% after heart failure(P0.01).The antibody mean titer of rats increased from(1∶19.49)±1.41 of pretreatment to(1∶152.79)±2.89 after heart failure(P0.01).(2) The autoantibody against β_3AR from HF rats reduced systolic and diastolic responses in adult isolated cardiomyocytes,which was not modified by pretreating myocytes with nadolol(β_1AR and β_2AR antagonist),but was nearly prevented by bupranolol(nonselective β_1AR,β_2AR and β_3AR antagonist) or β_3AR specific antigen.(3) The autoantibody decreased the beating rate in cultured neonatal rat cardiomyocytes,which persisted within 6 hours and was also not modified by pretreating myocytes with nadolol,but was nearly prevented by bupranolol or β_3AR specific antigen.CONCLUSION: Our present study demonstrated that the higher titer of the autoantibody against β_3AR generated by myocardial remodeling process during HF,which induced negative inotropic and chronotropic effects,may be a possibility of involvement in the pathophysiological mechanisms leading to heart failure.