血管紧张素Ⅱ和缬沙坦对血管内皮细胞AT1/AT2及eNOS 表达的调节作用

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (10): 1110-1114.

血管紧张素Ⅱ和缬沙坦对血管内皮细胞AT₁/AT₂及eNOS 表达的调节作用

王炎, 汪培华, 汪道文

华中科技大学同济医学院附属同济医院心内科, 武汉430030, 湖北

收稿日期:2004-06-29 修回日期:2004-08-30 出版日期:2004-10-26 发布日期:2020-11-23
通讯作者: 汪道文, 男, 博士后, 主任医师, 博士生导师, 研究方向:心血管疾病的基础与临床。Tel:027-83662842 E-mail:dwwang@tjh. tjmu. edu. cn
作者简介:王炎, 男, 博士, 主治医师, 研究方向:分子心脏病学。Tel:027-83663280 E-mail:newswangyan @hotmail.com

Effects of Angiotensin Ⅱ and valsartan on expression of AT₁/AT₂ and eNOS in human umbilical vein endothelial cells

WANG Yan, WANG Pei-Hua, WANG Dao-Wen

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China

Received:2004-06-29 Revised:2004-08-30 Online:2004-10-26 Published:2020-11-23

摘要/Abstract

摘要： 目的: 研究缬沙坦在血管内皮细胞中对血管紧张素Ⅱ(Ang Ⅱ) 受体I 型(AT₁) 和Ⅱ型(AT₂) 、一氧化氮合酶(eNOS) 的表达和一氧化氮(NO) 生成的影响。方法: 使用人脐静脉内皮细胞系ECV-304(HUVECs), 分为对照组、Ang Ⅱ组、缬沙坦组和Ang Ⅱ加缬沙坦组, 作用不同时间, 检测AT₁/AT₂ 的mRNA和蛋白表达、eNOS 的蛋白表达和NO 的生成。结果: 在HUVECs 细胞中未检测到AT₂的蛋白表达,Ang Ⅱ 、缬沙坦均显著抑制细胞中AT₁的mRNA 和蛋白表达, 且缬沙坦呈明显的剂量依赖效应, Ang Ⅱ作用36 h 显著抑制NO 的生成而合用缬沙坦可明显逆转该效应。结论: 在HUVECs 中缬沙坦可通过自身的结合下调AT₁, 并能逆转Ang Ⅱ长时间作用对NO生成的抑制作用, 提示缬沙坦可改善血管内皮细胞的功能。

关键词: 血管紧张素Ⅱ, 缬沙坦, 血管内皮细胞, 受体, 一氧化氮

Abstract: AIM: To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) and valsartan on the expression of Ang Ⅱ type 1 receptor (AT₁), Ang Ⅱ type 2 receptor (AT₂) and endothelial nitric oxide synthase (eNOS) and the synthesis of nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs, ECV304 cells).METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated by Ang Ⅱ or valsartan for various periods. The expression of AT₁/AT₂, eNOS and the production of NO were detected. Potential mechanism of the above effects was explored by using the relevant inhibitors of the signal molecules and antioxidants.RESULTS: Both Ang Ⅱ and valsartan significantly inhibited the mRNA and the protein expression of AT₁in HUVECs. The combination of the two drugs caused more significantly inhibitory effects. Ang Ⅱ showed a slightly promotive effect at first and a significantly inhibitory effect afterward on the expression of eNOS and synthesis of NO in HUVECs. MAPK inhibitor reversed the promotive effect whereas valsartan and antioxidant vitamine C significantly reversed the inhibitory effect.CONCLUSION: Valsartan can downregulate the expression of AT₁in HUVECs. Long time action of Ang Ⅱ can significantly inhibit the expression of eNOS and synthesis of NO in endothelial cells, while valsartan can significantly reverse this inhibitory effect.

Key words: angiotensin Ⅱ, valsartan, endothelial cells, receptor, endothelial nitric oxide synthase

中图分类号:

R962

王炎, 汪培华, 汪道文. 血管紧张素Ⅱ和缬沙坦对血管内皮细胞AT₁/AT₂及eNOS 表达的调节作用[J]. 中国临床药理学与治疗学, 2004, 9(10): 1110-1114.

WANG Yan, WANG Pei-Hua, WANG Dao-Wen. Effects of Angiotensin Ⅱ and valsartan on expression of AT₁/AT₂ and eNOS in human umbilical vein endothelial cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(10): 1110-1114.

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血管紧张素Ⅱ和缬沙坦对血管内皮细胞AT₁/AT₂及eNOS 表达的调节作用

Effects of Angiotensin Ⅱ and valsartan on expression of AT₁/AT₂ and eNOS in human umbilical vein endothelial cells

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