title: Macrophage infiltration and cellular proliferation in the non-ischemic kidney and heart following prolonged unilateral renal ischemia.
abstract: OBJECTIVE
  Although ischemic renal failure remains a major cause of morbidity and mortality, whether ischemic changes within a kidney might also have adverse effects on other organs has not been examined. Furthermore, given the protective effects of angiotensin II receptor (AT1) antagonism in renal ischemia, we considered whether a similar strategy might also modulate the response to acute renal insult.
  
  
  METHODS
  Unilateral renal artery ligation was performed in Sprague-Dawley rats, treated with or without the AT1 antagonist losartan (30 mg/kg/day). After 24 h of renal ischemia, changes in the contralateral kidney and heart were examined.
  
  
  RESULTS
  Contralateral non-ischemic kidneys displayed increased expression of platelet-derived growth factor-B (PDGF-B) in association with increased tubular cell proliferation. Gene expression for the macrophage chemokine osteopontin (OPN) was similarly increased along with substantial macrophage infiltration. In the heart, expression of OPN and macrophage numbers were increased. All of these changes, in both the heart and kidney were attenuated by losartan.
  
  
  CONCLUSIONS
  Rather than affecting a single organ, the present study demonstrates that after prolonged renal ischemia, the contralateral kidney and heart undergo changes in growth factor and chemokine expression, resulting in pathological proliferation and inflammation that can be modulated by blockade of the AT1 receptor.
authors.affiliation: Department of Medicine, St. Vincent's Hospital, University of Melbourne, Melbourne, Vic., Australia.
authors.forename: Hirobumi
authors.initials: H
authors.lastname: Tokuyama
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Renae M
authors.initials: RM
authors.lastname: Gow
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000208:Acute Disease; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D007511:Ischemia / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008026:Ligation; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012077:Renal Artery / Q000601:surgery
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D018809:Proliferating Cell Nuclear Antigen; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C506897:Spp1 protein, rat; D053495:Osteopontin; D019808:Losartan