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

被引:165
作者
Sun, Y
Zhang, JK
Zhang, JQ
Ramires, FJA
机构
[1] Univ Tennessee, Ctr Hlth Sci, Dept Med, Div Cardiovasc Dis, Memphis, TN 38163 USA
[2] Univ Tennessee, Ctr Hlth Sci, Dept Internal Med, Div Cardiol, Memphis, TN 38163 USA
关键词
kidney; fibrosis; myofibroblasts; angiotensin II; growth substances; rats;
D O I
10.1161/01.HYP.35.5.1078
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Studies have demonstrated that local angiotensin II (Ang II) generation is enhanced in repairing kidney and that ACE inhibition or AT(1) 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-beta 1 (TGF-beta 1) 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 mu g/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% AT(1), 408 AT(2)) at the 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, the enhanced expression of ACE, Ang II receptors, and TGF-beta 1 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-beta 1 synthesis.
引用
收藏
页码:1078 / 1084
页数:7
相关论文
共 29 条
  • [1] ANDERSON S, 1993, J AM PHYSL, V265, pF477
  • [2] PREVENTION OF EXPERIMENTAL CYCLOSPORINE-INDUCED INTERSTITIAL FIBROSIS BY LOSARTAN AND ENALAPRIL
    BURDMANN, EA
    ANDOH, TF
    NAST, CC
    EVAN, A
    CONNORS, BA
    COFFMAN, TM
    LINDSLEY, J
    BENNETT, WM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1995, 269 (04) : F491 - F499
  • [3] FIBROSIS CAUSES PROGRESSIVE KIDNEY FAILURE
    COHEN, EP
    [J]. MEDICAL HYPOTHESES, 1995, 45 (05) : 459 - 462
  • [4] DAEMEN MJA, 1995, WOUND HEALING CARDIO, P23
  • [5] CHARACTERIZATION OF CARDIAC ANGIOTENSIN CONVERTING ENZYME (ACE) AND INVIVO INHIBITION FOLLOWING ORAL QUINAPRIL TO RATS
    FABRIS, B
    YAMADA, H
    CUBELA, R
    JACKSON, B
    MENDELSOHN, FAO
    JOHNSTON, CI
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1990, 100 (03) : 651 - 655
  • [6] PRESENCE OF MODIFIED FIBROBLASTS IN GRANULATION TISSUE AND THEIR POSSIBLE ROLE IN WOUND CONTRACTION
    GABBIANI, G
    RYAN, GB
    MAJNO, G
    [J]. EXPERIENTIA, 1971, 27 (05): : 549 - &
  • [7] HALL CE, 1965, LAB INVEST, V14, P285
  • [8] Intracellular third loop domain of angiotensin II type-2 receptor - Role in mediating signal transduction and cellular function
    Hayashida, W
    Horiuchi, M
    Dzau, VJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (36) : 21985 - 21992
  • [9] TISSUE-SPECIFIC ACTIVATION OF CARDIAC ANGIOTENSIN CONVERTING ENZYME IN EXPERIMENTAL HEART-FAILURE
    HIRSCH, AT
    TALSNESS, CE
    SCHUNKERT, H
    PAUL, M
    DZAU, VJ
    [J]. CIRCULATION RESEARCH, 1991, 69 (02) : 475 - 482
  • [10] Delayed treatment with enalapril halts tubulointerstitial fibrosis in rats with obstructive nephropathy
    Ishidoya, S
    Morrissey, J
    McCracken, R
    Klahr, S
    [J]. KIDNEY INTERNATIONAL, 1996, 49 (04) : 1110 - 1119