title: Resistance to ischemic acute renal failure in the Brown Norway rat: a new model to study cytoprotection.
abstract: BACKGROUND
  An in vivo model of intrinsic resistance to ischemia could be invaluable to define how specific pathways to injury or putative protectors from injury affect the severity of acute renal failure (ARF). The purpose of this study was to determine whether separate rat strains had differential sensitivity to renal ischemia, characterize the extent of protection, and begin to define differences in gene expression that might impact on the severity of ARF.
  
  
  METHODS
  The sensitivity to 45 minutes of renal ischemia in Sprague-Dawley rat (SD) was compared with 2 lines of Brown-Norway rats (BN/Mcw, BN/Hsd). Constitutive and inducible stress protein expression was compared between strains.
  
  
  RESULTS
  At 24 hours' reperfusion, SD rats had higher creatinine (3.4 mg/dL), elevated Na and water excretion, and proximal tubule necrosis. Both strains of BN rats were resistant to loss of renal function (Scr = 0.9 mg/dL at 24 hours' reflow) and had preserved renal morphology. BN rats had no redistribution of Na,K-ATPase into detergent-soluble cortical extracts found early (15 minutes) after ischemia in SD rats. Hsc73 expression did not differ between strains and was not induced by ischemia. Compared with SD, induction of Hsp25 and 72 by renal ischemia was blunted in both BN strains. Constitutive Hsp25 was higher in both BN-Mcw and BN-Hsd compared with SD rat kidney. Constitutive Hsp72 was significantly higher only in BN-Mcw kidneys. Immunohistochemistry showed baseline Hsp72 and 25 expression was increased in proximal tubules of BN-Mcw versus SD.
  
  
  CONCLUSIONS
  BN rat kidney is resistant to ischemic injury and provides a new model for studying cytoprotective mechanisms. Initial study of strain-specific gene expression suggests particular stress proteins are among the potential mechanisms contributing to protection against ARF.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. dbasile@mcw.edu
authors.forename: David P
authors.initials: DP
authors.lastname: Basile
authors.forename: Deborah
authors.initials: D
authors.lastname: Donohoe
authors.forename: Xia
authors.initials: X
authors.lastname: Cao
authors.forename: Scott K
authors.initials: SK
authors.lastname: Van Why
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007511:Ischemia / Q000209:etiology; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013045:Species Specificity
chemical_list: D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494373:Hspa8 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase