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 system have been identified to date. Down-regulation of the biologically active 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 biological and clearance (NPR-C) receptors in target tissue may explain this increase.


OBJECTIVE
The aim of this study was to investigate the regulation of NPR-C receptors on platelets, in patients with HF.


METHODS
Eighteen patients with 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 binding sites were derived by saturation assays on platelet suspensions using 125I-ANP as radioligand.


RESULTS
B(max) increased as a function of the severity 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
The increase in density of 'clearance' receptors in severe HF is theoretically consistent with the reduction in cardiac natriuretic peptide biological activity, as well as the increase in metabolic clearance rate. This suggests that clearance receptor blockade may be of potential therapeutic value in HF.
Andreassi
M G
MG
CNR Institute of Clinical Physiology, Area della Ricerca, Via Moruzzi, 1, 56100 Pisa, Italy.
Del Ry
S
S
Palmieri
C
C
Clerico
A
A
Biagini
A
A
Giannessi
D
D
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000032:analysis; D001792:Blood Platelets / Q000737:chemistry*; D002908:Chronic Disease; D006152:Cyclic GMP / Q000096:biosynthesis*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017461:Receptors, Atrial Natriuretic Factor / Q000032:analysis / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015854:Up-Regulation
D015415:Biomarkers; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP