Both cell surface and internalized beta-adrenoceptors are reduced in the failing myocardium

To study myocardial beta-adrenoceptor internalization in heart failure, we measured beta-adrenoceptor density in the particulate, light vesicle and supernatant fractions of ventricular tissue of dogs with experimental right ventricular failure and sham-operated dogs. Tissue was fractionated by centrifugation, and beta-adrenoceptors were measured by [125I]iodocyanopindolol binding. Compared to sham-operated controls, beta-adrenoceptors were reduced in all fractions of right ventricular tissue from heart failure animals. Thus, the decreased surface (particulate fraction) receptors observed cannot be explained by internalization alone, and must be associated with altered receptor synthesis or degradation.