The origin of urinary angiotensins in humans.
To examine whether urinary angiotensin (ANG) I and II excretion responds 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 20 mg of enalapril twice daily. Infusion rates were 4, 8, 16, and 32 pmol/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, urinary 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. In 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 volunteers taking 400, 200, or 20 mmol of NaCl daily. In contrast to the considerable effects on plasma ANG I and ANG II and renal hemodynamics, 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 did not affect urinary ANG I and ANG II. These data suggest that urinary ANG I and ANG II originate from an intrarenal source. The independency of sodium intake and ANG-converting enzyme make the juxtaglomerular apparatus as the site responsible for the production of this ANG unlikely.
Vos
P F
PF
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Boer
P
P
Braam
B
B
Koomans
H A
HA
D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage / Q000097:blood / Q000652:urine*; D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood / Q000652:urine*; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011863:Radioimmunoassay; D012964:Sodium / Q000652:urine; D012982:Sodium, Dietary / Q000008:administration & dosage
D012982:Sodium, Dietary; D000804:Angiotensin II; D004656:Enalapril; D000803:Angiotensin I; D012964:Sodium; D007703:Peptidyl-Dipeptidase A