Antihypertensive effect of a 5-day infusion of atrial natriuretic factor in humans

Atrial natriuretic factor was infused in a low dose (0.2 microgram/min) during 5 days in six patients with essential hypertension. Atrial natriuretic factor infusion caused plasma levels of atrial natriuretic factor to increase from 49 +/- 10 to 106 +/- 19 pg/ml. Within 4 hours after the start of the atrial natriuretic factor infusion, urinary sodium excretion increased in all subjects. Sodium balance was regained after 24 hours with a net loss of 72.3 +/- 14.6 mmol. However, systolic as well as diastolic blood pressure started to decrease gradually in all subjects only after 12 hours of atrial natriuretic factor infusion, reaching a stable level after 36 hours with a decrease of 11.5 +/- 1.5% and 10.3 +/- 0.8%, respectively. Heart rate increased in parallel by 12.6 +/- 3.1%. Hematocrit rose 7.1 +/- 2.3%. After cessation of atrial natriuretic factor infusion, plasma atrial natriuretic factor levels, sodium balance, and hematocrit returned to baseline within 24 hours, whereas blood pressure slowly returned toward baseline values over 3 days. These data show that chronic atrial natriuretic factor infusion in patients with essential hypertension causes a negative sodium balance and a rise in hematocrit, followed by a smooth decrease in blood pressure with a rise in heart rate until a new equilibrium is reached after approximately 2 days. Thus, atrial natriuretic factor in low doses appears intimately involved in the regulation of sodium balance and blood pressure in humans. Moreover, these data suggest that atrial natriuretic factor-like substances will eventually become useful antihypertensive drugs.