Heterogeneous transmural distribution of β-adrenergic receptor subtypes in failing human hearts

Abstract

Background. Downregulation of myocardial βadrenergic receptor density does not occur in a spatially uniform distribution in patients with congestive heart failure. Rather, it results primarily from loss of receptors in the subendocardium. In patients with dilated cardiomyopathy, β1-receptors have been found to be downregulated selectively. These observations suggest that considerable transmural heterogeneity in the distribution of β-adrenergic receptor subtypes exists in the failing human heart. The present study was designed to test this hypothesis. Methods and Results. We used quantitative autoradiography of radioligand binding sites to measure the distribution of β-adrenergic receptor subtypes in transmural sections of left ventricular myocardium obtained from cardiac transplant patients with ischemic (n=13) and idiopathic dilated (n=12) cardiomyopathy and from 4 subjects with no history of congestive heart failure. Analysis of radioligand binding isotherms revealed a significant reduction in total β-adrenergic receptor density in hearts of patients with ischemic and idiopathic cardiomyopathy (20.3±1.9 and 18.2 ±2.0 fmol/nig protein, respectively, versus 40.0+11.4 in control subjects; P