Rat allele variation determines susceptibility to AngII-induced renal damage
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 pro...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publications
2011-12-01
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| Series: | Journal of the Renin-Angiotensin-Aldosterone System |
| Online Access: | https://doi.org/10.1177/1470320311415886 |
| _version_ | 1797281394365300736 |
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| author | Jelena Kamilic Inge Hamming A Titia Lely Ron Korstanje Ute Schulze Wilfred J Poppinga Anthony J Turner Nicola E Clarke Harry van Goor Gerjan J Navis |
| author_facet | Jelena Kamilic Inge Hamming A Titia Lely Ron Korstanje Ute Schulze Wilfred J Poppinga Anthony J Turner Nicola E Clarke Harry van Goor Gerjan J Navis |
| author_sort | Jelena Kamilic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T16:57:01Z |
| format | Article |
| id | doaj.art-548c4fbd2f4349f2951b097e142308fd |
| institution | Directory Open Access Journal |
| issn | 1470-3203 1752-8976 |
| language | English |
| last_indexed | 2024-03-07T16:57:01Z |
| publishDate | 2011-12-01 |
| publisher | SAGE Publications |
| record_format | Article |
| series | Journal of the Renin-Angiotensin-Aldosterone System |
| spelling | doaj.art-548c4fbd2f4349f2951b097e142308fd2024-03-03T03:42:17ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1470-32031752-89762011-12-011210.1177/1470320311415886Rat allele variation determines susceptibility to AngII-induced renal damageJelena Kamilic0Inge Hamming1A Titia Lely2Ron Korstanje3Ute Schulze4Wilfred J Poppinga5Anthony J Turner6Nicola E Clarke7Harry van Goor8Gerjan J Navis9Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The NetherlandsDepartment of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, The NetherlandsThe Jackson Laboratory, Bar Harbor, Maine, USADepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The NetherlandsDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The NetherlandsInstitute of Molecular and Cellular Biology, University of Leeds, Leeds, UKInstitute of Molecular and Cellular Biology, University of Leeds, Leeds, UKDepartment of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, The NetherlandsDepartment of Nephrology, University Medical Center Groningen, University of Groningen, The NetherlandsIntroduction : 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.https://doi.org/10.1177/1470320311415886 |
| spellingShingle | Jelena Kamilic Inge Hamming A Titia Lely Ron Korstanje Ute Schulze Wilfred J Poppinga Anthony J Turner Nicola E Clarke Harry van Goor Gerjan J Navis Rat allele variation determines susceptibility to AngII-induced renal damage Journal of the Renin-Angiotensin-Aldosterone System |
| title | Rat allele variation determines susceptibility to AngII-induced renal damage |
| title_full | Rat allele variation determines susceptibility to AngII-induced renal damage |
| title_fullStr | Rat allele variation determines susceptibility to AngII-induced renal damage |
| title_full_unstemmed | Rat allele variation determines susceptibility to AngII-induced renal damage |
| title_short | Rat allele variation determines susceptibility to AngII-induced renal damage |
| title_sort | rat allele variation determines susceptibility to angii induced renal damage |
| url | https://doi.org/10.1177/1470320311415886 |
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