Interaction of intravenous atrial natriuretic factor with furosemide in patients with heart failure

Abstract

Furosemide is frequently administered intravenously to patients with chronic heart failure. However, use of diuretics may cause neuroendocrine activation and by itself may not consistently afford diuresis. Atrial natriuretic factor (ANF) in pharmacologic doses is a vasodilator and has favorable neuroendocrinologic effects in patients with congestive heart failure. To examine whether exogenous ANF might enhance the effects of acute furosemide injection, we studied 14 patients with chronic stable heart failure and measured the effects of the combination of ANF and furosemide on hemodynamics, neuroendocrine activation, and urine output. Eight patients were randomly assigned to receive placebo plus furosemide (1.3 mg/kg intravenously). Six patients received ANF (2 μg/kg intravenously) plus furosemide at the same dose in a double-blind manner. The group receiving placebo plus furosemide exhibited a slight increase in mean arterial pressure (92 to 96 mm Hg; p < 0.03), systemic vascular resistance (1989 to 2271 dynes · sec · cm−5; p = 0.0007), and pulmonary capillary wedge pressure (22 to 24 mm Hg; p < 0.04) from baseline to 10 minutes. The group receiving ANF plus furosemide exhibited no change in mean arterial pressure and systemic vascular resistance from baseline to 10 minutes. Pulmonary capillary wedge pressure and mean pulmonary pressure were unchanged. In the group receiving placebo plus furosemide. Plasma renin activity and norepinephrine levels increased significantly from baseline to 10 minutes (plasma renin activity 12.3 ± 5 to 31.0 ± 10 ng/ml/hr; p < 0.01; plasma norepinephrine level 699 ± 100 to 876 ± 134 pg/ml; p < 0.01), whereas in the group receiving ANF plus furosemide no significant increase was noted in neuroendocrinologic activity. However, ANF did not further augment the diuretic response to furosemide. We conclude that pretreatment with ANF may blunt the mild systemic vasoconstrictor response to intravenous furosemide. The ability of ANF to attenuate activation of the renin-angiotensin and sympathetic nervous systems in response to furosemide may explain the lack of vasoconstriction in the ANF-treated group. There appears to be no important augmentation of natriuresis or diuresis when bolus ANF and intravenous furosemide are administered concomitantly to patients with congestive heart failure, although more patients will need to be studied to more precisely define these effects.