Distribution of j3-Adrenergic Receptors in Failing Human Myocardium

The density of f-adrenergic receptors is reduced in crude membranes prepared from failing human myocardium. We used quantitative autoradiography of radioligand binding sites in intact tissue slices to determine whether the total tissue content of receptors is reduced and to characterize the transmural distribution of receptors in cardiac myocytes and the coronary vasculature in hearts obtained from nine cardiac transplant patients with severe congestive failure. Binding of [t25Iodo]cyanopindolol to transmural slices ofhuman myocardium was rapid, saturable, stereoselective, and displaceable by agonists and antagonists with an appropriate rank order of potency. Binding isotherms in four normal and nine failing ventricles showed a significant reduction in the total tissue content of /3-receptors in failing myocardium (38.3+±2.0 fmol/mg protein) compared with normal tissue (52.4±+1.7 fmol/mg protein, p=0.038). In the normal ventricles, the greatest receptor density was observed autoradiographically in myocytic regions of the subendocardium. Receptor density of the coronary arterioles was approximately 70% of that in adjacent myocytic regions. The density of binding sites in both myocytic regions and arterioles was diminished in all regions of the failing ventricles, but down-regulation was due primarily to a selective reduction of ,B-receptors of subendocardial myocytes (63±-5% of subepicardial receptor density vs. 115±6% in controls, p<0.0001). These observations indicate that down-regulation occurs nonuniformly in the transmural distribution and thus is likely not related simply to elevated circulating catecholamine levels. (Circulation 1989;79:1214-1225)