Renal mechanisms of human alpha-atrial natriuretic peptide in man.

1. Eight normal volunteers were studied on two separate days after being dehydrated overnight. Each volunteer received a background intravenous infusion of arginine vasopressin (5.5 X 10(-7) i.u. kg-1 min-1) on both days and also received an intravenous infusion of human alpha-atrial natriuretic peptide (15 pmol kg-1 min-1) plus carrier on one day and carrier alone on the other. The ensuing changes in blood pressure, in the excretion of urinary solutes, and in the excretion of solute-free water were recorded. 2. The infusion of atrial peptide had a small hypotensive effect, and increased the rate of excretion of sodium but not of potassium. There were no significant changes of urinary osmolality or of creatinine clearance. 3. The infusion of atrial peptide increased the rate of solute-free water reabsorption and did so in direct proportion to its effect of increasing sodium excretion. 4. A further six normal, dehydrated volunteers were studied on each of two days after taking 500 mg of lithium carbonate on the previous evening. On one day, they received an intravenous infusion of human alpha-atrial natriuretic peptide (15 pmol kg-1 min-1) plus carrier and on the other day they received carrier alone. The excretion of urinary electrolytes and the creatinine clearance were recorded. 5. The infusion of atrial peptide produced significant increases in the rates of excretion of both sodium and lithium, but there were no such changes of creatinine clearance. 6. Another six normal volunteers were studied on each of two days. On each day they drank 2 l of water over 30 min and then water to replace their urinary losses. They also received loading doses and maintenance infusions of inulin and sodium para-aminohippurate. Once a full water diuresis had become established, each subject received an infusion of human alpha-atrial natriuretic peptide (15 pmol kg-1 min-1) plus carrier on one day and carrier alone on the other, exactly as before. The excretion of sodium and solute-free water, and the clearances of inulin and para-amino-hippurate were recorded. 7. The infusion of atrial peptide increased the rates of excretion of both sodium and solute-free water. It also increased the clearance of inulin, but not that of para-aminohippurate. 8. These results suggest that, in our volunteers, infusion of human alpha-atrial natriuretic peptide increases sodium excretion mainly by increasing the delivery of sodium along the renal tubule from sites upstream of the loop of Henle.(ABSTRACT TRUNCATED AT 400 WORDS)