Expression of angiotensinogen in proximal tubule as a function of glomerular filtration rate.
BACKGROUND
Proximal tubule (PT) angiotensinogen (AGT) is part of a tubular renin-angiotensin system (RAS) that participates in the regulation of sodium reabsorption along the entire nephron. Physiologic maneuvers affecting AGT expression in PT also affect systemic RAS. Here, we tested the hypothesis that PT AGT is regulated by increased glomerular filtration rate (GFR).


METHODS
Complete unilateral nephrectomy (UNX) in mice was used to induce a sustained increase in GFR in the remaining kidney. AGT expression was monitored by quantitative reverse transcription-polymerase chain reaction (RT-PCR). AGT protein in PT was investigated by semiquantitative histology. We also measured AGT concentration in plasma and in 24-hour urine by a specific enzyme-linked immunosorbent assay (ELISA).


RESULTS
Seven weeks after nephrectomy, UNX animals exhibited a 2-fold increase in tubular AGT mRNA (P <.001) compared with sham-operated control animals. The proportion of PT sections exhibiting AGT immunostaining was significantly increased at day 3 (P <.05), and remained elevated at seven weeks (UNX = 0.63 +/- 0.09, sham = 0.38 +/- 0.02, P <.01), revealing recruitment of AGT-producing cells along the PT. AGT excretion in final urine corrected for creatinine and kidney weight was also elevated by UNX at seven weeks (UNX = 209 +/- 42 pmol/mg/g, sham = 147 +/- 29 pmol/mg/g, P <.05), with no difference in plasma AGT between UNX and control animals.


CONCLUSIONS
These observations suggest that AGT expression in PT adapts in the long-term to changes in GFR. In the UNX model, urinary AGT excretion is also elevated as a consequence of increase in net tubular flow.
Gociman
Barbu
B
Department of Human Genetics, University of Utah, Health Sciences Center, Salt Lake City, 84112, USA.
Rohrwasser
Andreas
A
Lantelme
Pierre
P
Cheng
Tong
T
Hunter
Grant
G
Monson
Smith
S
Hunter
Jennifer
J
Hillas
Elaine
E
Lott
Paul
P
Ishigami
Tomoaki
T
Lalouel
J M
JM
D000222:Adaptation, Physiological; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000652:urine; D000818:Animals; D015870:Gene Expression; D005919:Glomerular Filtration Rate / Q000235:genetics* / Q000502:physiology*; D007687:Kidney Tubules, Proximal / Q000033:anatomy & histology / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009392:Nephrectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D000808:Angiotensinogen; D012083:Renin