title: Upregulation of autocrine-paracrine renin-angiotensin systems in chronic renovascular hypertension.
abstract: BACKGROUND
  The mechanism by which hypertension is maintained in renovascular hypertension remains poorly defined. Because plasma angiotensin II does not correlate with blood pressure in RVH, we postulated that activation of tissue-specific autocrine-paracrine renin-angiotensin systems may upregulate local production of angiotensin II and maintain hypertension in chronic RVH.
  
  
  METHODS
  RVH was induced with a two-kidney one-clip (2K1C) rat model. Animals were killed at 1 or 12 weeks after surgery (acute or chronic RVH). Angiotensin II was quantitated with radioimmunoassay. Angiotensin II-type 1 (AT(1)) receptor density was determined with immunoblotting and immunohistochemistry.
  
  
  RESULTS
  Blood pressure was significantly elevated in 2K1C animals compared with sham animals at 1 week (141 +/- 5 mm Hg versus 98 +/- 3 mm Hg; P <.0005) and at 12 weeks (164 +/- 14 mm Hg versus 110 +/- 7 mm Hg; P <.0005) after surgery. No significant difference was seen in plasma angiotensin II levels between 2K1C and control animals during acute (38.2 +/- 6.5 fmol/mL versus 27.6 +/- 6.8 fmol/mL; P = not significant) or chronic (40.1 +/- 17.4 fmol/mL versus 27.1 +/- 6.5 fmol/mL; P = not significant) RVH. During acute RVH, intrarenal angiotensin II was significantly increased in both the clipped (126.0 +/- 16.2 fmol/g versus 62.0 +/- 6.2 fmol/g; P <.005) and unclipped (78.9 +/- 6.3 fmol/g versus 39.9 +/- 2.5 fmol/g; P <.05) kidneys of 2K1C animals compared with control animals. Increased intrarenal angiotensin II levels persisted in chronic RVH in the clipped (147.4 +/- 37.7 fmol/g versus 59.2 +/- 8.7 fmol/g; P <.05) and unclipped (130.8 +/- 31.8 fmol/g versus 63.0 +/- 11.0 fmol/g; P <.05) kidneys of 2K1C animals compared with controls. Adrenal angiotensin II content of 2K1C animals was unchanged in acute RVH (493.7 +/- 51.4 fmol/g versus 522.6 +/- 80.5 fmol/g; P = not significant) but increased nearly three-fold over control animals during chronic RVH (1129.0 +/- 149.3 fmol/g versus 400.6 +/- 59.1 fmol/g; P <.0005). No significant difference in AT(1) receptor density was noted in renal tubules of clipped and unclipped kidneys or in the adrenal glands of 2K1C animals during acute or chronic RVH compared with control animals.
  
  
  CONCLUSIONS
  Tissue angiotensin II production is upregulated in the kidneys and adrenal glands in chronic RVH, and AT(1) receptor density is maintained in these tissues, providing a potential mechanism for maintenance of hypertension in RVH.
authors.affiliation: Division of Vascular Surgery and the Department of Surgery, Dallas Veterans Affairs Medical Center, and the University of Texas Southwestern Medical Center-Dallas, TX, USA.
authors.forename: Javid
authors.initials: J
authors.lastname: Sadjadi
authors.forename: Krishna
authors.initials: K
authors.lastname: Puttaparthi
authors.forename: M Burress
authors.initials: MB
authors.lastname: Welborn
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rogers
authors.forename: Orson
authors.initials: O
authors.lastname: Moe
authors.forename: G Patrick
authors.initials: GP
authors.lastname: Clagett
authors.forename: Richard H
authors.initials: RH
authors.lastname: Turnage
authors.forename: Moshe
authors.initials: M
authors.lastname: Levi
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Modrall
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication; D002908:Chronic Disease; D004195:Disease Models, Animal; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D011863:Radioimmunoassay; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D011945:Receptors, Angiotensin; D000804:Angiotensin II