Molecular forms of atrial natriuretic factor in normal and failing human myocardium

Background. Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart. Methods and Results. We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and α, β, and γ ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200 -fold. Analysis of molecular forms of ANF demonstrated significant increases in the γ and β forms in the left atrial appendage of failing hearts. α, β, and γ ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form ãANF. Conclusions. These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the β and γ ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.