PLASMA-LEVELS AND MOLECULAR-FORMS OF PROATRIAL NATRIURETIC PEPTIDES IN HEALTHY-SUBJECTS AND IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

A specific and sensitive radioimmunoassay (RIA) for the N-terminal fra gment of proatrial natriuretic peptide (NproANP) was developed. Antise rum raised in rabbits against a mixture enriched with prohormone was 1 00% cross-reactive with human proANP(1-30). Plasma concentrations of p roANP(1-30) and ANP immunoreactivities (ir-) were simultaneously measu red in healthy subjects and patients with congestive heart failure (CH F; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasm a levels of both ir-proANP(1-30) and ir-ANP were detected in CHF patie nts. Circulating ir-ANP levels were elevated in New York Heart Associa tion functional Classes II and III patients but not in Class I patient s. However, plasma levels of ir-proANP(1-30) were higher in asymptomat ic patients than in healthy subjects, and markedly increased in patien ts of Classes II and III. Analysis of ir-proANP(1-30) by ge filtration chromatography or reverse-phase high pressure liquid chromatography r evealed a 10 kDa peptide circulating as a distinct entity. These findi ngs indicate that: (i) the most probable form of NproANP in human plas ma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir- proANP(1-30) levels is more pronounced than the variation in plasma ir -ANP. Thus, NproANP plasma levels may prove to be a more sensitive mar ker of left ventricular dysfunction than ANP.