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Altered renal expression of angiotensin II receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats.
- Source :
-
American journal of nephrology [Am J Nephrol] 2010; Vol. 32 (3), pp. 249-261. Date of Electronic Publication: 2010 Aug 06. - Publication Year :
- 2010
-
Abstract
- Background: The susceptibility to fibrosis and progression of renal disease is mitigated by inhibition of the renin-angiotensin system (RAS). We hypothesized that activation of the intrarenal RAS predisposes to renal fibrosis in aging.<br />Methods: Intrarenal expression of angiotensin II type 1 (AT(1)R), type 2 (AT(2)R), and (pro)renin receptors, ACE and ACE-2, as well as pro- and antioxidant enzymes were measured in 3-month-old (young), 14-month-old (middle-aged), and 24-month-old (old) male Sprague-Dawley rats.<br />Results: Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT(1)R /AT(2)R ratios were increased in middle-aged (cortical 1.6-fold, medullary 5-fold) and old rats (cortical 2-fold, medullary 4-fold). Similarly, (pro)renin receptor expression was increased in middle-aged (cortical 2-fold, medullary 3-fold) and old (cortical 5-fold, medullary 3-fold) rats. Cortical ACE was increased (+35%) in old rats, whereas ACE-2 was decreased (-50%) in middle-aged and old rats. NADPH oxidase activity was increased (2-fold), whereas antioxidant capacity and expression of the mitochondrial enzyme manganese superoxide dismutase (cortical -40%, medullary -53%) and medullary endothelial nitric oxide synthase (-48%) were decreased in old rats.<br />Conclusion: Age-related intrarenal activation of the RAS preceded the development of severe renal fibrosis, suggesting that it contributes to the increased susceptibility to renal injury observed in the elderly.<br /> (Copyright © 2010 S. Karger AG, Basel.)
- Subjects :
- Angiotensin-Converting Enzyme 2
Animals
Disease Susceptibility
Fibrosis
Kidney Cortex metabolism
Kidney Diseases etiology
Kidney Medulla metabolism
Male
Nitric Oxide metabolism
Oxidative Stress
Rats
Rats, Sprague-Dawley
Renin metabolism
Superoxide Dismutase metabolism
Transforming Growth Factor beta metabolism
Aging physiology
Kidney Cortex pathology
Kidney Diseases metabolism
Kidney Medulla pathology
Peptidyl-Dipeptidase A metabolism
Receptors, Angiotensin metabolism
Renin-Angiotensin System physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9670
- Volume :
- 32
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of nephrology
- Publication Type :
- Academic Journal
- Accession number :
- 20689271
- Full Text :
- https://doi.org/10.1159/000318607