Circulating /3-Atrial Natriuretic Factor in Congestive Heart Failure in Humans

Background. P-Atrial natriuretic factor ((-ANF) is an antiparallel dimer of et-ANF (a-ANF) with diminished cyclic GMP generation in vitro. To date, the presence of f3-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 #-ANF in severe CHF, to correlate plasma #-ANF with the degree of ventricular dysfunction, and to investigate the role of human plasma and atrial tissue in the degradation of (3-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. a-ANF and (-ANF in nonextracted plasma were separated by gel filtration chromatography using a P-6 column. Right atrial tissue samples (n=S) were collected from a different group of patients at the time of open-heart surgery. 'II P-ANF and I1' ANF were incubated with atrial tissue or plasma. The corresponding peak areas of P-ANF were determined by Tamaya Digital Planimeter. P-ANF represented 61% of total plasma ANF in CHF patients and was not detected in normal human plasma. The elevation of j-ANF correlated with the severity of ventricular dysfunction. Thirty percent of 13-ANF and 100%o a-ANF were converted to smaller peptide fragments in atrial tissue with no conversion in plasma. Conclusions. (3-ANF is the principal form of circulating ANF in patients with severe CHF and correlates with the degree of left ventricular dysfunction. 13-ANF is not generated from cv-ANF and may be degraded rapidly in atrial tissue to smaller peptide fragments that do not occur in plasma. As 13-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. (Circulation. 1993;88:1016-1020.)