Up-regulation of 'clearance' receptors in patients with chronic heart failure: a possible explanation for the resistance to biological effects of cardiac natriuretic hormones

Background: Three specific receptors for the cardiac natriuretic peptide sy stem have been identified to date. Down-regulation of the biologically acti ve binding sites (i.e. NPR-A and NPR-B) could explain the blunted response to cardiac natriuretic hormones observed in heart failure (HF), but not the increased metabolic clearance rate. Variations in the ratio between biolog ical and clearance (NPR-C) receptors in target tissue may explain this incr ease. Aim: The aim of this study was to investigate the regulation of NPR-C receptors on platelets, in patients with HF. Methods: Eighteen patients wi th HF (NYHA class: I-II, n = 8; III-IV, n = 10) and 18 age-matched healthy subjects were studied. The affinity constant (K-d) and density (B-max) of b inding sites were derived by saturation assays on platelet suspensions usin g I-125-ANP as radioligand. Results: B-max increased as a function of the s everity of disease: 21.3 +/- 3.3 fmol/10(9) cells in class III-IV, 11.7 +/- 2.2 in class I-II, and 11.6 +/- 1.1 in controls, respectively (P = 0.0179 for class III-IV vs. controls and P = 0.0451 vs. NYHA I-II). Conclusions: T he increase in density of 'clearance' receptors in severe HF is theoretical ly consistent with the reduction in cardiac natriuretic peptide biological activity, as well as the increase in metabolic clearance rate. This suggest s that clearance receptor blockade may be of potential therapeutic value in HIT. (C) 2001 European Society of Cardiology. All rights reserved.