HETEROGENEOUS TRANSMURAL DISTRIBUTION OF BETA-ADRENERGIC-RECEPTOR SUBTYPES IN FAILING HUMAN HEARTS

Citation
Sl. Beau et al., HETEROGENEOUS TRANSMURAL DISTRIBUTION OF BETA-ADRENERGIC-RECEPTOR SUBTYPES IN FAILING HUMAN HEARTS, Circulation, 88(6), 1993, pp. 2501-2509
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiac & Cardiovascular System",Hematology
Journal title
ISSN journal
0009-7322
Volume
88
Issue
6
Year of publication
1993
Pages
2501 - 2509
Database
ISI
SICI code
0009-7322(1993)88:6<2501:HTDOBS>2.0.ZU;2-C
Abstract
Background. Downregulation of myocardial beta-adrenergic receptor dens ity does not occur in a spatially uniform distribution in patients wit h congestive heart failure. Rather, it results primarily from loss of receptors in the subendocardium. In patients with dilated cardiomyopat hy, beta 1-receptors have been found to be downregulated selectively. These observations suggest that considerable transmural heterogeneity in the distribution of beta-adrenergic receptor subtypes exists in the failing human heart. The present study was designed to test this hypo thesis. Methods and Results. We used quantitative autoradiography of r adioligand binding sites to measure the distribution of beta-adrenergi c receptor subtypes in transmural sections of left ventricular myocard ium 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 i sotherms revealed a significant reduction in total beta-adrenergic rec eptor density in hearts of patients with ischemic and idiopathic cardi omyopathy (20.3+/-1.9 and 18.2+/-2.0 fmol/mg protein, respectively, ve rsus 40.0+/-11.4 in control subjects; P<.01 for both). Loss of the bet a 1-subtype accounted for 86% of the total reduction in beta-receptor density in failing hearts. Despite the significant decreases in overal l tissue receptor content, the densities of total beta-receptors and b eta-receptor subtypes in subepicardial myocytes were equivalent in fai ling and control hearts. However, in contrast to control hearts, in wh ich the transmural distribution of total and beta 1-receptors was unif orm (endocardial: epicardial receptor density ratios, 0.97+/-0.14 and 1.0+/-0.2, respectively), hearts of patients with ischemic and idiopat hic dilated cardiomyopathy had significantly lower total beta-receptor and beta 1-receptor densities in the subendocardium (ratios, 0.66+/-0 .06 and 0.46+/-0.09 for total and beta 1-receptors, respectively, in i schemic cardiomyopathy and 0.60+/-0.08 and 0.52+/-0.11 in dilated card iomyopathy; P<.001 for all values compared with a ratio of 1). Thus, b eta 1:beta 2 receptor density ratios were markedly decreased in the su bendocardium of ischemic and idiopathic dilated left ventricles compar ed with control hearts. Conclusions. A significant transmural gradient in the density of myocardial beta 1-adrenergic receptors exists in th e hearts of patients with ischemic and dilated cardiomyopathy, resulti ng in a markedly altered beta 1:beta 2 receptor density ratio in the s ubendocardium.