Open AccessRatAceallele variation determines susceptibility to AngII-induced renal damage
Author(s) -
Jelena Kamilić,
Inge Hamming,
A. Titia Lely,
Ron Korstanje,
Ute Schulze,
W. J. Poppinga,
Anthony J. Turner,
Nicola E. Clarke,
Harry van Goor,
Gerjan Navis
Publication year - 2011
Publication title -
jraas. journal of the renin-angiotensin-aldosterone system/journal of the renin-angiotensin-aldosterone system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 46
eISSN - 1752-8976
pISSN - 1470-3203
DOI - 10.1177/1470320311415886
Subject(s) - medicine , endocrinology , angiotensin ii , allele , renin–angiotensin system , proteinuria , angiotensin converting enzyme , kidney , blood pressure , chemistry , biology , genetics , gene
Introduction: 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. Conclusion: 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.