The cardiac release and total body and renal clearances and the hemodynamic, renal and endocrine effects of increasing doses of atrial natriuretic peptide were investigated in 12 patients with severe chronic congestive heart failure. Immunoreactive arterial plasma levels of atrial natriuretic peptide were 10-fold higher than normal and there was no correlation between aortic atrial natriuretic peptide and cardiac filling pressures. The heart released atrial natriuretic peptide into the coronary sinus. The kidney, though a major clearance site, accounted for only 33% of the total body clearance. Administration of 0.3 μg/kg per min atrial natriuretic peptide produced significant changes in heart rate (95 ± 4 to 85 ± 4 beats/min) and mean arterial (92 ±8 to 77 ± 9 mm Hg), right atrial (13 ± 3 to 8 ± 2 mm Hg) and mean pulmonary artery occluded (27 ± 3 to 14 ± 3 mm Hg) pressures. Atrial natriuretic peptide increased cardiac index (2.25 ± 0.18 to 2.83 ± 0.3 liters/min per m²) and stroke work index (21 ± 1.5 to 29 ± 3.4 g/m²), whereas systemic vascular resistance (1,424 ± 139 to 1,033 ± 97 dynes-s-cm⁻⁵) decreased.

Infusion of 0.1 μg/kg per min atrial natriuretic peptide increased urinary flow 128%, fractional excretion of sodium 133% and fractional excretion of potassium 35%. The filtration fraction increased from 29 ± 2 to 31 ± 4%. This represented a disproportionate rise in glomenuar filtration rate over renal plasma Bow. Plasma aldosterone and norepinephrine decreased whereas plasma renin activity remained unchanged. In association with these hemodynamic, excretory and endocrine changes, the urinary excretion of cyclic guanosine monophosphate doubled. Placebo had no effect. These results showed that, despite high circulating levels of atrial natriuretic peptide, administration of this hormone in heart failure is associated with potentially beneficial hemodynamic, renal and endocrine effects.