Negative inotropic effects of autoantibodies against β 3 ‐adrenoceptor in patients with dilated cardiomyopathy on isolated cardiomyocyte

The aim of the present study was to evaluate the biological role of autoantibodies against the second extracellular loop of β 3 ‐adrenoceptor (β 3 ‐AR) from the sera of patients with dilated cardiomyopathy (DCM). The anti‐β 3 ‐AR autoantibodies from the sera of DCM induced agonistic negative contractile responses decreasing cell shortening/cell length (3.86±0.31%), the maximal velocity of shortening (−0.47±0.07μm/s) and relengthening (0.17±0.02μm/s) (p<0.0001 n=10), prolonging the time to 90% peak shortenings (0.27±0.06ms, p<0.05 n=10)and to 90% relengthening (0.55±0.04ms, p<0.01 n=10) of adult rat isolated cardiomyocytes, which can not be modified by pretreating myocytes with Nadolol (β 1 ‐AR and β 2 ‐AR antagonist) but nearly be prevented by Bupranolol (nonselective β‐AR antagonist) or β 3 ‐AR specific antigen. Our results demonstrated for the first time that the anti‐β 3 ‐adrenoceptor autoantibodies in the sera of patients with DCM exhibited remarkable negative inotropic on cardiomyocytes, and suggesting that the involvement of immunologic mechanism by cardiac receptor antibodies in the pathogenesis and symptomatology of DCM and may contribute to a new therapeutic clue for the disease.