title: Apoptosis and proliferation of mesangial cells isolated from kidneys undergoing compensatory growth following contralateral nephrectomy: role of the renin-angiotensin system.
abstract: BACKGROUND
  Contralateral nephrectomy stimulates compensatory growth of the remaining kidney. Intensive growth is frequently associated with increased apoptosis. The proliferation and apoptosis of cultured rat mesangial cells isolated from the remaining kidney following contralateral nephrectomy were evaluated. The involvement of the renin-angiotensin system was concomitantly assessed.
  
  
  METHODS
  Apoptosis was assessed by TUNEL assay and hematoxylin staining, proliferation by (3)H-thymidine incorporation, angiotensin-II (A-II) production by RIA, bradykinin synthesis by specific EIA, and AT-1/AT-2 receptor mRNA expression by RT-PCR.( 125)I-A-II labeling was applied for AT-1/AT-2 receptor density evaluation.
  
  
  RESULTS
  Apoptosis of unstimulated control cultures progressively increased from a baseline of 2.02+/-0.55% to 8.3+/-1.19% in 30-min and 12.8+/-4.11% in 24-h cultures (p<0.0001 in each comparison), accompanied by augmented cell proliferation and both could be abolished by captopril treatment. Endogenous A-II synthesis was increased in postnephrectomy cultures. Exogenous A-II enhanced apoptosis of control, but not of postnephrectomy cells. Bradykinin synthesis was elevated in cultures treated with captopril, but not with losartan or PD123319. AT-1 mRNA was increased 24 h following nephrectomy. Total A-II receptor density was decreased 30 min and 24 h following nephrectomy, while blockade of AT-1/AT-2 receptors was ineffective.
  
  
  CONCLUSIONS
  1. Contralateral nephrectomy stimulates apoptosis and proliferation of mesangial cells in the remaining kidney via increased endogenous A-II. 2. The mechanism by which A-II triggers apoptosis and proliferation of mesangial cells is not related to the AT-1/AT-2 receptor pathway. 3. The effects of angiotensin-II can be abolished by ACE inhibition and are, at least in part, mediated via bradykinin activity.
authors.affiliation: Nephrology Division, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Israel. labnefro@asaf.health.gov.il
authors.forename: Joshua
authors.initials: J
authors.lastname: Weissgarten
authors.forename: Sylvia
authors.initials: S
authors.lastname: Berman
authors.forename: Shai
authors.initials: S
authors.lastname: Efrati
authors.forename: Micha
authors.initials: M
authors.lastname: Rapoport
authors.forename: Mirel
authors.initials: M
authors.lastname: Cohn
authors.forename: David
authors.initials: D
authors.lastname: Modai
authors.forename: Zhan
authors.initials: Z
authors.lastname: Averbukh
mesh_terms: D000803:Angiotensin I / Q000235:genetics / Q000378:metabolism; D000804:Angiotensin II / Q000096:biosynthesis / Q000494:pharmacology; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001920:Bradykinin / Q000096:biosynthesis; D002216:Captopril / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects; D009392:Nephrectomy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D001920:Bradykinin