Molecular weight heterogeneity of plasma-ANF in cardiovascular disease

Structural differences of circulating ANF may partly explain why the physiological response of the heart in controlling volume/pressure loading in cardiovascular disease states remains insufficient in spite of elevated ANF plasma levels. Structural analysis of plasma ANF immunoreactivity was performed by means of gel permeation of plasma extracts subsequent to radioimmunoassay. ANF plasma levels in hypertensive patients or patients with congestive heart failure (CHF) were significantly elevated as compared to normotensive controls or cirrhotics. (61.7 +/- 13.2 or 81.5 +/- 32.7 versus 9.6 +/- 1.0 or 10.3 +/- 1.3 fmol/ml, p less than 0.01). In CHF patients, ANF plasma concentrations were significantly correlated to right atrial and pulmonary capillary wedge pressures. ANF release was stimulated by head-out water immersion both in normotensive controls and cirrhotic patients. No higher molecular weight forms were detected in plasma of control subjects. 15,000-dalton ANF, in addition to 3080-dalton ANF, was present in plasma of hypertensive patients and, in trace amounts, of cirrhotic patients. In some CHF patients, elevated ANF plasma levels predominantly comprised higher molecular weight forms of approx. 15,000 daltons MW, in addition to considerable amounts of ANF immunoreactivity presumably bound to larger proteins that eluted in the void volume. The data suggest that a dysregulation of post-translational processing of ANF may contribute to the pathophysiology of cardiovascular disease.