Atriopeptin III. A potent natriuretic, diuretic, and hypotensive agent in rats with chronic renal failure

Chronic renal failure is frequently associated with volume overload, resulting in hypertension and, in some cases, congestive heart failure. Atriopeptin III (AP III), a 24-amino acid atrial peptide, is a potent vasodilator and natriuretic/diuretic agent in normal rats. An infusion of AP III at 0.2 microgram/kg per min for 60 min produced dramatic responses in animals with chronic renal failure (5/6 nephrectomy 4 wk before study). Systemic blood pressure fell 20% by the end of infusion. A pronounced rise in glomerular filtration rate (24%) was maintained during the infusion period when urine flow rate was stable (35-60 min), even though renal blood flow was unchanged from base line. Urinary volume increased 4.4-fold and sodium excretion increased 9 to 12-fold during the infusion. Fractional excretion of sodium ranged between 9 and 15% in those animals whose initial GFR values were lower than 0.5 ml/min. We conclude that AP III is a potent natriuretic/diuretic agent in rats with reduced renal mass, presumably exerting that effect predominantly through increases in GFR. This agent may well be useful in the treatment of volume overload in patients with chronic renal failure.