Author + information
- Received September 28, 1987
- Revision received February 10, 1988
- Accepted February 18, 1988
- Published online July 1, 1988.
- César R. Molina, MD∗,
- Michael B. Fowler, MBBS,
- Shelley Mccrory, BSRN,
- Craig Peterson, BS,
- Bryan D. Myers, MD,
- John S. Schroeder, MD, FACC and
- Ferid Murad, MD, PhD
- ↵∗Address for reprints: César R. Molina, MD, Divisions of Cardiology and Clinical Pharmacology, Stanford University Medical Center, Stanford, California 94305.
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.
☆ This study was presented in part at the American Federation of Clinical Research Meetings, May 1987, San Diego, California. This work was supported by Grants AM30787. HL28474 from the National Institutes of Health, Bethesda, Maryland; the Veterans Administration, Washington, D.C.; the Council for Tobacco Research and Wyeth Laboratories. Dr. Molina is a recipient of a Robert Wood Johnson Scholarship (9832).
- Received September 28, 1987.
- Revision received February 10, 1988.
- Accepted February 18, 1988.