Amlodipine suppresses Ang-II-induced endothelium dysfunction by diminishing ROCK1 expression. (17th February 2016)

• Record Type: Journal Article
• Authors: Xu, Rulin; Cai, Anping; Zheng, Dongdan; Qiu, Ruofeng; Li, Liwen; Zhou, Yingling; Feng, Yingqing; Mai, Weiyi
• Is Part Of: Clinical and experimental hypertension. Volume 38:Number 2(2016)
• Page Start: 166
• Page End: 172
• Publication Date: 2016-02-17
• Subjects: Rho-associated kinase -- endothelial function -- amlodipine; Hypertension -- Chemotherapy -- Periodicals; Hypotensive agents -- Periodicals; 616.132
• DOI: 10.3109/10641963.2015.1081212
• Languages: English
• ISSNs: 1064-1963

Abstract

Abstract: Objective : To investigate the effects and mechanisms of amlodipine therapy on endothelium dysfunction induced by angiotensin-II (Ang-II) stimulation. Methods : Human umbilical vein endothelial cells (HUVECs) were used and divided into five groups: Blank control, Ang-II (10 −6 mol/L), levorotatory amlodipine (5 × 10 −6 mol/L) + Ang-II (10 −6 mol/L), dextrorotatory amlodipine (5 × 10 −6 mol/L) + Ang-II (10 −6 mol/L) and racemic amlodipine (5 × 10 −6 mol/L) + Ang-II (10 −6 mol/L) groups. Twenty-four hours later, HUVECs were collected for evaluating endothelial nitric oxide synthase (eNOS), p-eNOS, rho-associated kinase 1 (ROCK1), Bcl-2 and Bax expressions. Nitric oxide (NO) concentration within endothelium was also detected. Flow cytometry was conducted to assess HUVECs apoptosis. Results : With 24 hours of Ang-II stimulation, compared to blank control group, expressions of eNOS and p-eNOS and NO production were significantly reduced in Ang-II group ( p < 0.05), while adding amlodipine-protected HUVECs from dysfunction induced by Ang-II. In contrast, ROCK1 expression was promoted in Ang-II group ( p < 0.05). However, the expression of ROCK1 in each enantiomer of amlodipine group was significantly decreased ( p < 0.05). Compared to levorotatory amlodipine group, the magnitude of ROCK1 diminishment in dextrorotatory amlodipine group was more profound ( p < 0.05). The pro-survival protein (Bcl-2) was significantly upregulated, while the pro-apoptotic protein (Bax) was significantly downregulated in three amlodipine groups compared to Ang-II group. Flow cytometry revealed that amlodipine therapy could protect HUVECs from apoptosis, and no significant difference between three amlodipine groups was observed. Conclusion : Amlodipine could suppress Ang-II-induced endothelial dysfunction and apoptosis through diminishing ROCK1 expression.