Altered renal expression of angiotensin ii receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats

Ivonne Hernandez Schulman, Ming Sheng Zhou, Adriana V. Treuer, Kiranmai Chadipiralla, Joshua M. Hare, Leopoldo Raij

Research output: Contribution to journalArticle

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. Methods: Intrarenal expression of angiotensin II type 1 (AT 1R), type 2 (AT2R), 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. Results: Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT1R /AT2R 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. 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.

Original languageEnglish (US)
Pages (from-to)249-261
Number of pages13
JournalAmerican Journal of Nephrology
Volume32
Issue number3
DOIs
StatePublished - Sep 2010
Externally publishedYes

Fingerprint

Angiotensin Receptors
Renin
Fibrosis
Kidney
Renin-Angiotensin System
Antioxidants
Nitric Oxide Synthase Type III
NADPH Oxidase
Enzymes
Fibronectins
Angiotensin II
Superoxide Dismutase
Sprague Dawley Rats
Disease Progression
Wounds and Injuries

Keywords

  • Aging
  • Angiotensin
  • Fibrosis
  • Kidney disease
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Nephrology

Cite this

Altered renal expression of angiotensin ii receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats. / Schulman, Ivonne Hernandez; Zhou, Ming Sheng; Treuer, Adriana V.; Chadipiralla, Kiranmai; Hare, Joshua M.; Raij, Leopoldo.

In: American Journal of Nephrology, Vol. 32, No. 3, 09.2010, p. 249-261.

Research output: Contribution to journalArticle

Schulman, Ivonne Hernandez ; Zhou, Ming Sheng ; Treuer, Adriana V. ; Chadipiralla, Kiranmai ; Hare, Joshua M. ; Raij, Leopoldo. / Altered renal expression of angiotensin ii receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats. In: American Journal of Nephrology. 2010 ; Vol. 32, No. 3. pp. 249-261.
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T1 - Altered renal expression of angiotensin ii receptors, renin receptor, and ACE-2 precede the development of renal fibrosis in aging rats

AU - Schulman, Ivonne Hernandez

AU - Zhou, Ming Sheng

AU - Treuer, Adriana V.

AU - Chadipiralla, Kiranmai

AU - Hare, Joshua M.

AU - Raij, Leopoldo

PY - 2010/9

Y1 - 2010/9

N2 - 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. Methods: Intrarenal expression of angiotensin II type 1 (AT 1R), type 2 (AT2R), 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. Results: Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT1R /AT2R 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. 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.

AB - 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. Methods: Intrarenal expression of angiotensin II type 1 (AT 1R), type 2 (AT2R), 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. Results: Old rats manifested glomerulosclerosis and severe tubulointerstitial fibrosis with increased fibronectin and TGF-β expression (7-fold). AT1R /AT2R 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. 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.

KW - Aging

KW - Angiotensin

KW - Fibrosis

KW - Kidney disease

KW - Nitric oxide

KW - Oxidative stress

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