The pathophysiologic role of atrial natriuretic factor and other neuroendocrine variables in relation to serum sodium and renal function was evaluated in 15 conscious dogs with severe chronic ventricular pacing-induced heart failure (250 beats/min for 5.1 +/- 0.4 weeks). Six sham-operated dogs observed over an 8 week period served as controls. Development of heart failure was characterized by a progressive increase in plasma norepinephrine, renin activity and aldosterone from control values of 293 +/- 15 pg/ml, 1.4 +/- 0.4 ng/ml per h and 124 +/- 42 pg/ml, respectively, to 1,066 +/- 96 pg/ml, 10.2 +/- 2.4 ng/ml per h and 577 +/- 151 pg/ml (all p less than 0.01), respectively, at severe heart failure. In contrast to other neuroendocrine variables, plasma atrial natriuretic factor increased from a control level of 243 +/- 74 pg/ml to a peak concentration of 724 +/- 149 pg/ml (p less than 0.01) at 2 weeks, then declined and plateaued at twice the level of the control value as severe heart failure developed. At severe heart failure, serum sodium decreased from 147 +/- 0.6 to 141.8 +/- 2.1 mmol/liter (p less than 0.05), whereas urea increased from 6.0 +/- 0.5 to 7.8 +/- 0.6 mmol/liter (p less than 0.05). The change in serum sodium concentration correlated with plasma renin activity and aldosterone (r = -0.77, -0.88, respectively, both p less than 0.01), but not with norepinephrine or atrial natriuretic factor. When sinus rhythm was restored, 14 dogs were observed for 48 to 72 h and 8 dogs were followed up for another 4 weeks after cessation of pacing.(ABSTRACT TRUNCATED AT 250 WORDS)