Circulating β-atrial natriuretic factor in congestive heart failure in humans

Background. β-Atrial natriuretic factor (β-ANF) is an antiparallel dimer of α-ANF (α-ANF) with diminished cyclic GMP generation in vitro. To date, the presence of β-ANF in the circulation of humans with severe congestive heart failure (CHF) remains controversial. The current study was designed to determine the presence and magnitude of circulating β-ANF in severe CHF, to correlate plasma β-ANF with the degree of ventricular dysfunction, and to investigate the role of human plasma and atrial tissue in the degradation of β-ANF. Methods and Results. Venous plasma samples were obtained from patients (n=12) with severe CHF and normal volunteers (n=8). Total plasma ANF was measured by radioimmunoassay. α-ANF and β-ANF in nonextracted plasma were separated by gel filtration chromatography using a P-6 column. Right atrial tissue samples (n=5) were collected from a different group of patients at the time of open-heart surgery. ¹²⁵I β-ANF and I¹²⁵ ANF were incubated with atrial tissue or plasma. The corresponding peak areas of β- ANF were determined by Tamaya Digital Planimeter. β-ANF represented 61% of total plasma ANF in CHF patients and was not detected in normal human plasma. The elevation of β-ANF correlated with the severity of ventricular dysfunction. Thirty percent of β-ANF and 100% α-ANF were converted to smaller peptide fragments in atrial tissue with no conversion in plasma. Conclusions. β-ANF is the principal form of circulating ANF in patients with severe CHF and correlates with the degree of left ventricular dysfunction. β-ANF is not generated from α-ANF and may be degraded rapidly in atrial tissue to smaller peptide fragments that do not occur in plasma. As β-ANF is reported to have reduced biological action, the current studies may support the conclusion that the ANF system in CHF has reduced functional activity despite increases in circulation concentrations.