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Monocyte chemoattractant protein-1 and macrophage infiltration in hypertensive kidney injury.

AbstractBACKGROUND:
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.
CONCLUSION:
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.
AuthorsK F Hilgers, A Hartner, M Porst, M Mai, M Wittmann, C Hugo, D Ganten, H Geiger, R Veelken, J F Mann
JournalKidney international (Kidney Int) Vol. 58 Issue 6 Pg. 2408-19 (Dec 2000) ISSN: 0085-2538 [Print] United States
PMID11115074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Angiotensin Receptor Antagonists
  • Antihypertensive Agents
  • Chemokine CCL2
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin
  • Tetrazoles
  • Valsartan
  • Valine
Topics
  • Angiotensin Receptor Antagonists
  • Animals
  • Antihypertensive Agents (pharmacology)
  • Blood Pressure
  • Chemokine CCL2 (analysis, genetics)
  • Chemotaxis, Leukocyte (immunology)
  • Gene Expression (physiology)
  • Hypertension, Renal (drug therapy, immunology, pathology)
  • Kidney (chemistry, immunology, pathology)
  • Kidney Failure, Chronic (immunology)
  • Macrophages (cytology, immunology)
  • Monocytes (cytology, immunology)
  • Nephrosclerosis (drug therapy, immunology, pathology)
  • RNA, Messenger (analysis)
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Rats, Mutant Strains
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, Angiotensin (physiology)
  • Tetrazoles (pharmacology)
  • Valine (analogs & derivatives, pharmacology)
  • Valsartan

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