title: Angiotensin II infusion ameliorates the early phase of a mesangioproliferative glomerulonephritis.
abstract: BACKGROUND
  Inhibition of the renin-angiotensin system slows the progression of chronic renal disease.
  
  
  METHODS
  To test whether angiotensin II (Ang II) infusion aggravates or ameliorates an acute glomerulonephritis, the peptide was infused (200 ng/min by osmotic minipump) in rats with an anti-thymocyte antibody-induced glomerulonephritis (ATS).
  
  
  RESULTS
  Ang II significantly increased blood pressure. Following injection of the antibody, similar glomerular binding of rabbit IgG and rat complement C3 was detected in ATS and Ang II+ATS rats, indicating no differences in delivery and binding of the antibody. Ang II infusion, however, induced a significant reduction in glomerular monocyte infiltration, cell proliferation and matrix expansion in nephritic rats compared to rats with nephritis without Ang II. The antiproliferative effect of Ang II was inhibited by the Ang II type 1 (AT1) receptor blocker irbesartan, but not by the AT2 receptor blocker PD 123319, indicating that this effect was likely transduced by AT1 receptors. Norepinephrine infusion (600 ng/min) produced a similar degree of hypertension, but did not affect glomerular proliferation in nephritic rats. Ang II induced the glomerular expression of the cell cycle inhibitor p27KIP1 and of transforming growth factor-beta (TGF-beta) and inhibited expression of monocyte chemotactic protein 1 (MCP-1).
  
  
  CONCLUSIONS
  Ang II surprisingly ameliorates glomerular monocyte infiltration, proliferation and matrix expansion in ATS nephritis. Ang II-mediated induction of cyclin kinase inhibitors and TGF-beta may contribute to the protection of the glomerulus from inflammatory injury by inducing cell cycle arrest and attenuating activation of local and recruited cells. Alternatively, Ang II might protect the kidney at least in part by less inflow of disease activators due to reduction of renal blood flow. Therefore, activation of the renin-angiotensin system may have protective effects in certain pathophysiological situations.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Hamburg, Martinistrasse 52, 20246 Hamburg, Germany. wenzel@uke.uni-hamburg.de
authors.forename: Ulrich O
authors.initials: UO
authors.lastname: Wenzel
authors.forename: Friedrich
authors.initials: F
authors.lastname: Thaiss
authors.forename: Udo
authors.initials: U
authors.lastname: Helmchen
authors.forename: Rolf A K
authors.initials: RA
authors.lastname: Stahl
authors.forename: Gunter
authors.initials: G
authors.lastname: Wolf
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003176:Complement C3 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005109:Extracellular Matrix / Q000378:metabolism; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology*; D007074:Immunoglobulin G / Q000378:metabolism; D007260:Infusion Pumps; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D003176:Complement C3; D007074:Immunoglobulin G; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D050760:Cyclin-Dependent Kinase Inhibitor p27; D009638:Norepinephrine