RENAL INJURY FROM ANGIOTENSIN-II - MEDIATED HYPERTENSION
RENAL INJURY FROM ANGIOTENSIN-II - MEDIATED HYPERTENSION
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DOI：
10.1161/01.hyp.19.5.464
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发表时间：
1992-05-01
期刊：
影响因子：
8.3
通讯作者：
SCHWARTZ, SM
中科院分区：
文献类型：
--
作者：
JOHNSON, RJ;ALPERS, CE;SCHWARTZ, SM
血管紧张素II(Ang II)介导的高血压可诱导全身血管的血管平滑肌细胞肥大和增殖，但Ang II对肾脏内固有细胞群的影响尚不清楚。我们用小剂量(200 ng/min)给大鼠注射血管紧张素Ⅱ14天，造成中度高血压(平均收缩压156-172毫米汞柱)。血管紧张素转换酶II组大鼠肾小动脉表现为局灶性损伤，伴有纤维素样坏死和中层增生，而肾小球毛细血管仅表现为少见的节段性透明蛋白。血管平滑肌细胞的增殖明显([H-3]胸腺嘧啶核苷掺入增加四到20倍)，而肾小球细胞的增殖程度在血管紧张素Ⅱ注射的大鼠中最小。相反，Ang II在肾小球的主要作用是增加系膜细胞α-平滑肌肌动蛋白和内脏肾小球上皮细胞结蛋白的表达。注射血管紧张素Ⅱ的大鼠也出现局灶性肾小管间质损伤，表现为肾小管萎缩和扩张，管型形成，间质单核细胞浸润，轻度间质纤维化，IV型胶原沉积增多。增殖细胞核抗原免疫组织化学染色显示，损伤与远端小管、集合管和间质细胞的增殖有关，并伴有间质损伤区域血小板衍生生长因子B链信使RNA的增加(原位杂交定位)。肾间质细胞也经历了表型改变，表达了α-平滑肌肌动蛋白。注入载体的对照组大鼠没有表现出肾小管损伤、增殖或表型改变。因此，在导致中度高血压的剂量下，Ang II会导致明显的血管、肾小球和肾小管间质损伤，表现为细胞增殖、白细胞聚集、表型改变和正常情况下与平滑肌细胞相关的蛋白质上调，以及间质纤维化。
Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [H-3]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.