ROLE OF ANGIOTENSIN-II IN THE TUBULOINTERSTITIAL FIBROSIS OF OBSTRUCTIVE NEPHROPATHY
ROLE OF ANGIOTENSIN-II IN THE TUBULOINTERSTITIAL FIBROSIS OF OBSTRUCTIVE NEPHROPATHY
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DOI：
10.1016/0272-6386(95)90167-1
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发表时间：
1995-07-01
影响因子：
13.2
通讯作者：
MORRISSEY, J
中科院分区：
文献类型：
--
作者：
KLAHR, S;ISHIDOYA, S;MORRISSEY, J
慢性单侧输尿管梗阻导致受累肾间质纤维化。血管紧张素转换酶抑制剂依那普利和血管紧张素II受体拮抗剂SC-51316都能改善梗阻肾小管上皮细胞外基质蛋白的增加。阻断血管紧张素II的合成或血管紧张素II不能与其受体结合，可减少未治疗大鼠梗阻肾中转化生长因子β和IV型胶原mRNA水平的升高。未处理大鼠或血管紧张素II受体拮抗剂处理大鼠的阻塞肾脏中存在单核细胞/巨噬细胞浸润。与此相反，这种渗透几乎完全没有在阻塞的肾脏用依那普利治疗的大鼠。与血管紧张素II受体拮抗剂相比，依那普利对梗阻性肾病中所见的巨噬细胞浸润的不同作用的原因尚未阐明。我们的结论是，血管紧张素转换酶抑制剂（依那普利）和血管紧张素II的受体拮抗剂改善肾小管间质纤维化，完全单侧输尿管梗阻大鼠。我们认为血管紧张素II水平的升高在输尿管梗阻后肾小管间质纤维化的发展中起重要作用。(C)1995年由国家肾脏基金会，公司。
Chronic unilateral ureteral obstruction results in interstitial fibrosis of the affected kidney. Both an angiotensin-converting enzyme inhibitor, enalapril, and an angiotensin II receptor antagonist, SC-51316, ameliorate the increased production of extracellular matrix protein in the tubulointerstitium of the obstructed kidney. Blockade of angiotensin II synthesis or inability of angiotensin II to bind to its receptor lessened the increased levels of mRNA for transforming growth factor-beta and collagen IV found in the obstructed kidney of untreated rats. A monocyte/macrophage infiltration was present in the obstructed kidney of untreated rats or rats treated with the angiotensin II receptor antagonists. In contrast, this infiltrate was almost completely absent in the obstructed kidney of rats treated with enalapril. The reason for this different effect of enalapril compared with the angiotensin II receptor antagonist on the macrophage infiltrate seen in obstructive nephropathy has not been elucidated. We conclude that both an angiotensin-converting enzyme inhibitor (enalapril) and a receptor antagonist of angiotensin II ameliorate the tubulointerstitial fibrosis that follows complete unilateral ureteral obstruction in the rat. We suggest that an increased level of angiotensin II has a major role in the development of tubulointerstitial fibrosis following ureteral obstruction. (C) 1995 by the National Kidney Foundation, Inc.