The character of the atrial natriuretic response: pressure and volume effects

Synthetic atrial natriuretic factor (ANF) was compared to the well-characterized diuretics hydrochlorothiazide and furosemide in rats. While ANF was markedly more potent than either agent, its natriuretic potency more closely resembled hydrochlorothiazide. Probenecid, a drug that competes with diuretics such as furosemide for secretion into the renal tubular lumen and thereby decreases diuretic effectiveness, did not interfere with the natriuretic actions of ANF. In rats, continuous infusion of ANF resulted in a bell-shaped dose-response relationship. Above a dose of approximately 100 pmol/kg per min, the response waned and at the highest doses studies, 1-2 nmol/kg per min, urinary sodium excretion fell below control levels. A similar bell-shaped dose-response curve was observed in anaesthetized volume-expanded monkeys. During euvolaemia, conscious monkeys showed a marked fall in blood pressure without concomitant natriuresis. The blood pressure was sustained for the 3-h duration of the ANF infusion. One percent body weight volume expansion blunted the fall in blood pressure in these monkeys and the restored natriuretic response did not wane during 3-h infusion. When the fall in blood pressure was prevented by angiotensin II infusion in conscious euvolaemic monkeys, the natriuretic response to ANF was expressed.