title: Rat Ace allele variation determines susceptibility to AngII-induced renal damage.
abstract: BACKGROUND
  Ace b/l polymorphism in rats is associated with differential tissue angiotensin-converting enzyme (ACE) expression and activity, and susceptibility to renal damage. Same polymorphism was recently found in outbred Wistar rat strain with b allele accounting for higher renal ACE, and provided a model for studying renin-angiotensin-aldosterone system (RAAS) response behind the innate high or low ACE conditions.
  
  
  METHODS
  We investigated the reaction of these alleles on chronic angiotensin II (AngII) infusion. Wistar rats were selected to breed male homozygotes for the b (WU-B) or l allele (WU-L) (n = 12). For each allele, one group (n = 6) received AngII infusion via an osmotic minipump (435 ng/kg/min) for 3 weeks. The other group (n = 6) served as a control.
  
  
  RESULTS
  WU-B had higher ACE activity at baseline then WU-L. Interestingly, baseline renal ACE2 expression and activity were higher in WU-L. AngII infusion induced the same increase in blood pressure in both genotypes, no proteinuria, but caused tubulo-interstitial renal damage with increased α-SMA and monocyte/macrophage influx only in WU-B (p < 0.05). Low ACE WU-L rats did not develop renal damage.
  
  
  CONCLUSIONS
  AngII infusion causes proteinuria-independent renal damage only in rats with genetically predetermined high ACE while rats with low ACE seemed to be protected against the detrimental effect of AngII. Differences in renal ACE2, mirroring those in ACE, might be involved.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The Netherlands. j.kamilic@umcg.nl
authors.forename: Jelena
authors.initials: J
authors.lastname: Kamilic
authors.forename: Inge
authors.initials: I
authors.lastname: Hamming
authors.forename: A Titia
authors.initials: AT
authors.lastname: Lely
authors.forename: Ron
authors.initials: R
authors.lastname: Korstanje
authors.forename: Ute
authors.initials: U
authors.lastname: Schulze
authors.forename: Wilfred J
authors.initials: WJ
authors.lastname: Poppinga
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Turner
authors.forename: Nicola E
authors.initials: NE
authors.lastname: Clarke
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Gerjan J
authors.initials: GJ
authors.lastname: Navis
mesh_terms: D000483:Alleles; D000804:Angiotensin II; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020022:Genetic Predisposition to Disease; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D000804:Angiotensin II; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2