Local angiotensin II and transforming growth factor-β1 in renal fibrosis of rats

Yao Sun, Jiakun Zhang, John Q. Zhang, Felix J.A. Ramires

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

Studies have demonstrated that local angiotensin II (Ang II) generation is enhanced in repairing kidney and that ACE inhibition or AT1 receptor blockade attenuates renal fibrosis. The localization of ACE and Ang II receptors and their relationship to collagen synthesis in the injured kidney, however, remain uncertain. Using a rat model of renal injury with subsequent fibrosis created with chronic elevations in circulating aldosterone (ALDO), we examined the distribution and binding density of ACE and Ang II receptors in repairing kidneys, as well as their anatomic relationship to transforming growth factor-β1 (TGF-β1) mRNA, type I collagen mRNA, collagen accumulation, and myofibroblasts. Two groups of animals (n = 7 in each group) were studied: (1) normal rats served as controls, and (2) uninephrectomized rats received ALDO (0.75 μg/h SC) and 1% NaCl in drinking water for 6 weeks. Compared with control rats, in ALDO-treated rats we found (1) significantly (P<0.01) increased blood pressure, reduced plasma renin activity, and increased plasma creatinine levels, (2) diffuse fibrosis in both renal cortex and medulla, (3) abundant myofibroblasts at these sites of fibrosis, (4) significantly increased (P<0.01) binding density of ACE and Ang II receptors (60% AT1, 40% AT2) at the sites of fibrosis, and (5) markedly increased (P<0.01) expression of TGF-β1 and type I collagen mRNAs at these same sites. Thus, in this rat model of renal repair, the enhanced expression of ACE, Ang II receptors, and TGF-β1 is associated with renal fibrosis. Ang II generated at the sites of repair appears to have autocrine/paracrine functions in the regulation of renal fibrous tissue formation alone or through its stimulation of TGF-β1 synthesis.

Original languageEnglish (US)
Pages (from-to)1078-1084
Number of pages7
JournalHypertension
Volume35
Issue number5
DOIs
StatePublished - Jan 1 2000

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Transforming Growth Factors
Angiotensin II
Fibrosis
Kidney
Angiotensin Receptors
Aldosterone
Myofibroblasts
Collagen Type I
Messenger RNA
Collagen
Renin
Drinking Water
Creatinine
Blood Pressure
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Internal Medicine

Cite this

Local angiotensin II and transforming growth factor-β1 in renal fibrosis of rats. / Sun, Yao; Zhang, Jiakun; Zhang, John Q.; Ramires, Felix J.A.

In: Hypertension, Vol. 35, No. 5, 01.01.2000, p. 1078-1084.

Research output: Contribution to journalArticle

Sun, Yao ; Zhang, Jiakun ; Zhang, John Q. ; Ramires, Felix J.A. / Local angiotensin II and transforming growth factor-β1 in renal fibrosis of rats. In: Hypertension. 2000 ; Vol. 35, No. 5. pp. 1078-1084.
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