It remains unclear whether the levels of atrial natriuretic factor (ANF) observed in chronic CHF are appropriate for the magnitude of elevations in atrial pressures. Specifically, it is not known whether acute increases in atrial pressure in CHF can result in further significant increases in circulating ANF. The present study was designed to test the hypothesis that in chronic CHF there is an attenuated relation between circulating ANF and atrial pressure such that the heart is unable to respond to further increases in atrial pressure with appropriate increases in ANF. Cardiovascular hemodynamics and plasma levels of ANF were measured at baseline and after rapid right ventricular pacing (RRVP) to produce acute (n = 10, 25 minutes RRVP) and chronic (n = 7, 14-16 days RRVP) CHF. Acute saline volume expansion was then performed in each group to determine the response of circulating ANF to acute increases in atrial pressure in both acute and chronic CHF. In chronic CHF, right atrial pressure was much higher than in acute CHF (8.5 +/- 0.9 vs. 3.4 +/- 1.3 mm Hg, p less than 0.05); however, circulating ANF was not greater in chronic as compared with acute CHF (385 +/- 73 vs. 500 +/- 89 pg/ml), which is consistent with an attenuated release of ANF in chronic CHF. In response to volume expansion, right atrial pressure increased in both acute (3.4 +/- 1.3 to 12.1 +/- 7 mm Hg) and chronic (8.5 +/- .9 to 13.3 +/- 1.0 mm Hg) CHF.(ABSTRACT TRUNCATED AT 250 WORDS)