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Strain differences in angiotensin-converting enzyme and angiotensin II type I receptor expression. Possible implications for experimental chronic renal transplant failure

Departments of Pathology and Laboratory Medicine, University Hospital Groningen, a.smit-van.oosten{at}med.rug.nl

Robert H Henning

Department of Clinical Pharmacology, University Hospital Groningen, Groningen, The Netherlands

Harry van Goor

Departments of Pathology and Laboratory Medicine, University Hospital Groningen

Background The Fisher to Lewis (F-L) model of renal transplantation (Rtx) is widely used. Rtx from F to L without immunosuppressive treatment results in 50% survival, whereas L to F results in survival rates similar to syngrafts. When treated with an angiotensin-converting enzyme (ACE) inhibitor or antihypertensive triple therapy, renal damage is markedly reduced in F-L allografts. Despite similar reductions in blood pressure, the ACE inhibitor (ACE-I) is more effective than antihypertensive triple therapy, suggesting that the inhibition of intrarenal ACE plays an additional role in the attenuation of renal damage.

Methods In the present study, we investigated strain-related differences in intrarenal ACE activity between F and L rats and whether treatment with ACE-I in F-L allografted rats results in reduction of intrarenal ACE. Intrarenal ACE was measured by activity assays, immunohistochemistry and PCR.

Results In control kidneys from healthy F rats (n=8), we found a four-fold higher ACE activity than in native L rats (n=8, p<0.01). This was confirmed by a three-fold difference in ACE mRNA expression (n=5 for both, p<0.01). Using immunohistochemistry, we found strong tubular ACE expression in the F rat, whereas the L rat had no tubular ACE at all. In F-L allografts (n=9) we noted significant glomerulosclerosis and proteinuria after 34 weeks. Treatment with ACE-I in F-L (n=8) prevented the development of these changes. Although ACE mRNA and ACE protein expression were similar in treated and untreated allografts, intrarenal ACE activity was reduced by 50% in allografts with ACE-I.

Conclusion In conclusion, intrarenal levels of ACE may play a role in the development of renal damage in experimental chronic renal transplant failure.

Key Words: transplantation • kidney • ACE • AT1-receptor • chronic renal transplant failure • rat

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Journal of Renin-Angiotensin-Aldosterone System, Vol. 3, No. 1, 46-53 (2002)
DOI: 10.3317/jraas.2002.008


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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Smit-van Oosten, A. Articles by van Goor, H. Search for Related Content PubMed PubMed Citation Articles by Smit-van Oosten, A. Articles by van Goor, H. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Kidney Transplantation Social Bookmarking                         What's this?