LOCALIZATION OF THE SITE OF THE NATRURETIC ACTION OF SKF 525-A

¹ Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa

Infusion of SKF 525-A into the renal artery of the dog at rates of 1,2,4,8 and 16 mg/minute, during water diuresis, produced significant ipsilateral increases in urine volume, osmolar clearance, free water clearance and sodium excretion. Osmolar clearance increased as the rate of infusion was increased over the entire dose range studied. Up to 4 mg/minute the changes in urine volume appeared to be related to dose; however, at 8 and 16 mg/minute no further increases in volume were seen. As a result, free water clearance increased with dose only at the lower rates of infusion, thereafter the magnitude of the response was depressed with increasing dose. Sodium excretion increased gradually with doses of 1,2 and 4 mg/minute. With higher rates of administration the rate of sodium excretion increased sharply.

In hydropenic animals, infusion of SKF 525-A (4, 8 and 16 mg/min) increased urine volume, osmolar clearance and sodium excretion. Negative free water clearance (T^cH₂O) remained relatively unaffected by the drug.

It is concluded that tubular reabsorption of sodium in the proximal areas of the nephron is inhibited by low doses (1, 2 and 4 mg/min) of SKF 525-A, whereas higher rates of infusion (8 and 16 mg/min) inhibit sodium reabsorption in both proximal and distal areas. Furthermore, it would appear that the distal site of inhibition is beyond the ascending limb of the loop of Henle.