title: Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury.
abstract: BACKGROUND
  We investigated whether monocyte chemoattractant protein-1 (MCP-1) is expressed in hypertensive nephrosclerosis, and tested the effect of angiotensin II type 1 receptor blockade on MCP-1 expression and macrophage (MPhi) infiltration.
  
  
  METHODS
  Rats with two-kidney, one-clip (2K1C) hypertension with and without treatment with the angiotensin II type 1 receptor antagonist valsartan (3 mg/kg/day) were studied. In these animals as well as in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHR-SP), hypertensive mRen-2 transgenic rats (TGR), and respective control strains, MCP-1 expression in the kidney was investigated by Northern and Western blots and by immunohistochemistry. Glomerular and interstitial MPhis were counted.
  
  
  RESULTS
  In the nonclipped kidney of 2K1C rats, MCP-1 expression was elevated at 14 and 28 days when significant MPhi infiltration was present. MCP-1 was localized to glomerular endothelial and epithelial cells, interstitial and tubular cells, MPhis, and vascular smooth muscle cells. A similar pattern of MCP-1 staining was present in TGR kidneys, whereas MCP-1 expression was not increased in SHR and SHR-SP. Valsartan reduced but did not normalize blood pressure, blocked the induction of MCP-1 protein in 2K1C kidneys, and decreased interstitial MPhi infiltration significantly.
  
  
  CONCLUSIONS
  MCP-1 expression is increased in angiotensin II-dependent models of hypertensive nephrosclerosis and is temporally and spatially related to MPhi infiltration. The angiotensin II type 1 receptor mediates the induction of MCP-1.
authors: Department of Medicine IV, University of Erlangen-Nürnberg, Erlangen; Max-Delbrück-Center, Berlin-Buch, Germany. karl.hilgers@rzmail.uni-erlangen.de
authors: K F
authors: KF
authors: Hilgers
authors: A
authors: A
authors: Hartner
authors: M
authors: M
authors: Porst
authors: M
authors: M
authors: Mai
authors: M
authors: M
authors: Wittmann
authors: C
authors: C
authors: Hugo
authors: D
authors: D
authors: Ganten
authors: H
authors: H
authors: Geiger
authors: R
authors: R
authors: Veelken
authors: J F
authors: JF
authors: Mann
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D015870:Gene Expression / Q000502:physiology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D007668:Kidney / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D009400:Nephrosclerosis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D018932:Chemokine CCL2; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine