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Significance of α‐Human Atrial Natriuretic Polypeptide as a Hormone in Humans

The bolus injection of 50 μg and 100 μg of α-human atrial natriuretic polypeptide (a-hANP) in humans resulted in a significant and rapid increase of natriuresis, chloriuresis, and diuresis associated with an increase of endogenous creatinine clearance and a decrease of negative or positive free water clearance. The injection of this peptide also caused a significant fall in blood pressure, accompanied by an increase in heart rate. The concentration of α-hANP-like immunoreactivity in normal peripheral plasma was 37.7 ± 7.0 pg/ml (mean ± SEM). Plasma concentrations of α-hANP-like immunoreactivity in the coronary sinus in patients with heart diseases were three to 10 times higher than those in the peripheral vein, inferior vena cava, right atrium, pulmonary artery, and aorta. In these patients plasma α-hANP-like immunoreactivity was undetectable during the extracorporeal circulation at cardiovascular surgery. Gel permeation chromatography coupled with a radioimmunoassay for α-hANP revealed that α-hANP-like immunoreactivity in normal peripheral plasma was eluted at the position of authentic α-hANP without detectable amounts of high-molecularweight forms. The α-hANP-like immunoreactivity extracted from plasma taken from the coronary sinus also showed a single peak of α-hANP-like immunoreactivity co-eluting with α-hANP. Plasma ahANP-like immunoreactivity of normal subjects increased twofold in response to volume expansion with drip infusion of 2 L of physiological saline. These results indicate that α-hANP has rapid and potent natriuretic, diuretic, and hypotensive actions in humans and that α-hANP is the predominant form of α-hANP-like immunoreactivity in human plasma and is released from the heart. These characteristics suggest the physiological and pathophysiological significance of this peptide as a hormone in the control of volume and electrolyte balance and blood pressure in humans.