(Hypertension. 2000;35:1078.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Local Angiotensin II and Transforming Growth Factor-ß1 in Renal Fibrosis of Rats
From the Division of Cardiology, Department of Internal Medicine, University of Tennessee Health Sciences Center, Memphis, Tenn.
Correspondence to Yao Sun, MD, PhD, Department of Medicine, Division of Cardiovascular Diseases, 956 Court Ave, Room B310, Memphis, TN 38163.
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-ß1 (TGF-ß1) 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-ß1 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-ß1 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-ß1 synthesis.
Key Words: kidney • fibrosis • myofibroblasts • angiotensin II • growth substances • rats
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