Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production

Kidney Int. 2002 Feb;61(2):579-85. doi: 10.1046/j.1523-1755.2002.00155.x.


Background: In rats maintained on a high salt diet (H/S) to suppress basal renal angiotensinogen levels, angiotensin II (Ang II) infusion for 13 days increased renal angiotensinogen mRNA and protein, thus providing a mechanism for further augmentation of intrarenal Ang II levels. The present study tested the hypothesis that enhanced intrarenal angiotensinogen formation during Ang II infusion is reflected by secretion into the tubular fluid leading to increased urinary excretion of angiotensinogen (UAGT).

Methods: The effects of chronic Ang II infusion were examined on kidney and plasma Ang II levels and UAGT in male Sprague-Dawley rats maintained on an 8% salt diet for three weeks (N=10). Following one week on the H/S diet, Ang II (40 ng/min) was administered for two weeks via an osmotic minipump to one group (H/S + Ang II, N=5), while the remaining rats were sham-operated (H/S + Sham, N=5). Additionally, a control group was prepared with normal salt diet and sham-operation (N/S + Sham, N=5).

Results: H/S alone did not alter systolic blood pressure (BP) (103 +/- 2 vs. 104 +/- 2 mm Hg), while Ang II infusion to H/S rats significantly increased systolic BP from 103 +/- 2 to 154 +/- 2 after two weeks. Intrarenal Ang II content in H/S + Ang II was significantly greater than H/S + Sham (435 +/- 153 vs. 65 +/- 14 fmol/g). Ang II infusion significantly increased UAGT (4.0 +/- 0.5 vs. 1.0 +/- 0.2 nmol Ang I/day by radioimmunoassay of generated Ang I; 57 +/- 15 vs. 14 +/- 2 densitometric units by Western blotting analysis) compared to Sham. UAGT by radioimmunoassay was highly correlated with kidney Ang II content (r=0.79); but not with plasma Ang II concentration (r=0.20).

Conclusions: These data demonstrate that chronic Ang II infusion increases urinary excretion rate of angiotensinogen, and suggest that UAGT provides a specific index of intrarenal angiotensinogen production in Ang II-dependent hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / analysis
  • Angiotensin II / blood
  • Angiotensin II / pharmacology
  • Angiotensinogen / biosynthesis*
  • Angiotensinogen / urine*
  • Animals
  • Blood Pressure
  • Hypertension, Renal / metabolism
  • Kidney / chemistry
  • Kidney / metabolism*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Renin / blood
  • Renin-Angiotensin System / drug effects
  • Renin-Angiotensin System / physiology
  • Sodium Chloride, Dietary / pharmacology
  • Vasoconstrictor Agents / pharmacology


  • Sodium Chloride, Dietary
  • Vasoconstrictor Agents
  • Angiotensinogen
  • Angiotensin II
  • Renin