Alterations in serum sodium in relation to atrial natriuretic factor and other neuroendocrine variables in experimental pacing-induced heart failure

Abstract

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 < 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 < 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 < 0.05), whereas urea increased from 6.0 ± 0.5 to 7.8 ± 0.6 mmol/ liter (p < 0.05). The change in serum sodium concentration correlated with plasma renin activity and aldosterone (r = −0.77, −0.88, respectively, both p < 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. Recovery from heart failure was characterized by a return of all neuroendocrine variables, serum sodium and urea levels to control values by 48 to 72 h.The unique time profile of atrial natriuretic factor during the developing heart failure suggests that the circulating level of this hormone may not be sufficient to maintain circulatory homeostasis in advanced heart failure. The strong negative correlations among the change in serum sodium and plasma renin and aldosterone support the hypothesis proposed by previous clinical studies that hyponatremia in congestive heart failure is in part mediated by the activation of the renin-angiotensin system.