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Title: Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy. Implications for the pathogenesis of tubulointerstitial fibrosis.
Austin Authors: Gilbert, Richard E;Wu, L L;Kelly, D J;Cox, Allison J;Wilkinson-Berka, J L;Johnston, Colin I;Cooper, Mark E
Affiliation: Department of Medicine, University of Melbourne, Australia
Issue Date: 1-Aug-1999
Publication information: The American Journal of Pathology; 155(2): 429-40
Abstract: The finding that the systemic renin-angiotensin system (RAS) is not activated in most types of chronic renal disease has led to the suggestion that a local, intrarenal RAS may be an important determinant in the relentless progression of renal disease. Therefore, cell specific changes in various components of the RAS in response to renal mass reduction and angiotensin converting enzyme (ACE) inhibition were examined. Thirty Sprague-Dawley rats were randomly assigned to sham surgery, subtotal nephrectomy (STNx) alone or STNx treated with the ACE inhibitor, perindopril, and sacrificed after 12 weeks. In sham rats, renin mRNA and protein were only present in the juxtaglomerular apparatus. In contrast, in STNx kidneys, renin and angiotensin II expression were noted predominantly in renal tubular epithelial cells in association with overexpression of the prosclerotic cytokine, transforming growth factor-beta1 (TGF-beta1). In perindopril-treated STNx rats expression of renin and TGF-beta1 were similar to control animals. These finding indicate that following renal mass reduction there is pathological tubular expression of various components of the RAS. Furthermore, in contrast to the juxtaglomerular apparatus, tubular renin expression was reduced with ACE inhibition. These changes within the intrarenal RAS may be pathogenetically linked to the development of tubulointerstitial injury.
Gov't Doc #: 10433936
DOI: 10.1016/S0002-9440(10)65139-5
Type: Journal Article
Subjects: Angiotensin II.analysis.metabolism
In Situ Hybridization
Kidney.anatomy &
Kidney Tubules.anatomy &
Nephritis, Interstitial.metabolism
Peptidyl-Dipeptidase A.analysis.metabolism
Rats, Sprague-Dawley
Transforming Growth Factor alpha.analysis.metabolism
Transforming Growth Factor beta.analysis.metabolism
Appears in Collections:Journal articles

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