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Yao Sun, Jiakun Zhang, John Zhang, Karl T. Weber, O-25: Local angiotensin II and transforming growth factor-beta 1 in renal fibrosis of rats, American Journal of Hypertension, Volume 14, Issue S1, April 2001, Page 12A, https://doi.org/10.1016/S0895-7061(01)01342-5
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Abstract
Studies have demonstrated that local angiotensin II (AngII) generation is enhanced in repairing kidney and angiotensin converting enzyme (ACE) inhibition or AT1 receptor blockade attenuates renal fibrosis. The localization of ACE and AngII receptors and their relationship to collagen synthesis in the injured kidney, however, remains uncertain. Using a rat model of renal injury with subsequent fibrosis created by chronic elevations in circulating aldosterone (ALDO), we examined the distribution and binding density of ACE and AngII receptors in repairing kidneys, as well as their anatomic relationship to transforming growth factor (TGF)-beta 1 mRNA, type I collagen mRNA, collagen accumulation and myofibroblasts (myoFb). Two groups of animals (n=7/group) were studied: 1) normal rats served as controls; and 2) uninephrectomized rats received ALDO (0.75mg/hr sc) and 1% NaCl in drinking water for 6 weeks. Compared to controls, in ALDO-treated rats we found: 1) significantly (P<0.01) increased blood pressure and reduced plasma renin activity and increased plasma creatinine; 2) diffuse fibrosis in both renal cortex and medulla; 3) abundant myoFb at these sites of fibrosis, 4) significantly increased (P<0.01) binding density of ACE and AngII receptors (60% AT1: 40% AT2) at sites of fibrosis; and 5) markedly increased (P<0.01) expression of TGF-beta 1 and type I collagen mRNAs at these same sites. Thus, in this rat model of renal repair, enhanced expression of ACE, AngII receptors and TGF-beta 1 are associated with renal fibrosis. AngII generated at sites of repair appears to have autocrine/paracrine functions in regulating renal fibrous tissue formation alone or through its stimulation of TGF-beta 1 synthesis.
- hypertension
- angiotensin-converting enzyme
- aldosterone
- transforming growth factor beta
- angiotensin ii
- creatinine
- fibrosis
- collagen
- collagen type i
- cortex of kidney
- plasma
- rna, messenger
- sodium chloride
- transforming growth factors
- kidney
- procedures on kidney
- rats
- renal trauma
- autocrine
- paracrine
- myofibroblasts
- collagen synthesis
- plasma renin activity
- potable water