THE ORIGIN OF URINARY ANGIOTENSINS IN HUMANS

To examine whether urinary angiotensin (ANG) I and II excretion respon ds to changes in plasma ANG I and ANG II, ANG I or ANG II was infused in seven healthy subjects pretreated with a 340-mmol sodium diet and 2 0 mg of enalapril twice daily. Infusion rates were 4, 8, 16, and 32 pm ol/kg per minute for ANG I and 1, 4, and 8 pmol/kg per minute for ANG II. Baseline ANG I and ANG II excretions averaged 10 and 20 fmol/min, respectively, which is approximately 0.3 and 5% of the filtered loads. Despite a 20-fold increase in plasma ANG I during ANG I infusion, uri nary ANG I did not increase. Similarly, the 30-fold increase in plasma ANG II during ANG II infusion was not followed by an increase in ANG II excretion, but in fact by a decrease in urinary ANG I and ANG II. I n a separate study, urinary ANG I and ANG II were measured before and after the oral administration of 20 mg of enalapril in eight healthy v olunteers taking 400, 200, or 20 mmol of NaCl daily. In contrast to th e considerable effects on plasma ANG I and ANG II and renal hemodynami cs, enalapril had no effect on urinary ANG I and ANG II. Variation of sodium intake had predictable effects on plasma ANG I and ANG II but d id not affect urinary ANG I and ANG II. These data suggest that urinar y ANG I and ANG II originate from an intrarenal source. The independen cy of sodium intake and ANG-converting enzyme make the juxtaglomerular apparatus as the site responsible for the production of this ANG unli kely.