Possible tubular site of action in anesthetized dogs of a synthetic alpha-human atrial natriuretic polypeptide.

Intrarenal arterial infusion of a synthetic alpha-human atrial natriuretic polypeptide (alpha-hANP) in a dose of 5.0 micrograms/min to anesthetized dogs led to a significant increase in urine flow and urinary excretion of electrolytes. Tubular sites of action of alpha-hANP were determined by using free water clearance techniques and in stop-flow experiments. During water diuresis, free water clearance did not increase in proportion to the increase in urine flow rate. Intrarenal administration of the peptide to dehydrated animals resulted in no change in solute-free water reabsorption, notwithstanding a significant increase in osmolar clearance. These data suggest that the peptide acts on the diluting segment of the ascending limb of Henle and also at the distal nephrons, findings which support data obtained in stop-flow experiments. Infusion of the peptide lowered inulin concentration and elevated sodium concentration in the stop-flow urine from the distal tubules and collecting duct. It is tentatively concluded that alpha-hANP produces potent diuretic and natriuretic responses by suppressing water and sodium transport in the distal portion of the nephron.