Nitric oxide synthesis-promoting effects of valsartan in human umbilical vein endothelial cells via the Akt/adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

被引:5
|
作者
Zhao, Yingshuai [1 ,2 ]
Wang, Liuyi [2 ,3 ]
He, Shanshan [1 ]
Wang, Xiaoyan [1 ]
Shi, Weili [1 ]
机构
[1] Zhengzhou Univ, Peoples Hosp, Dept Cardiol, Zhengzhou, Henan, Peoples R China
[2] Henan Prov Peoples Hosp, Dept Gen Med, Zhengzhou, Henan, Peoples R China
[3] Zhengzhou Univ, Peoples Hosp, Dept Gen Med, 07 Weiwu Rd, Zhengzhou 450000, Henan, Peoples R China
关键词
Valsartan; nitric oxide; protein kinase B; adenosine monophosphate-activated protein kinase; endothelial nitric oxide synthase; AMPK; RECEPTOR; HYPERTENSION; AGGREGATION; DYSFUNCTION; EXPRESSION; STRESS;
D O I
10.17305/bjbms.2017.1319
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Valsartan (VAL), an antagonist of angiotensin II receptor type 1, has antihypertensive and multiple cardiovascular protective effects. The pleiotropic functions of VAL are related to the increased synthesis and biological activity of intravascular nitric oxide (NO). In this study, the role and mechanisms of VAL in the synthesis of NO were examined in human umbilical vein endothelial cells (HUVECs). Ten mu mol/L of VAL was used to treat EA. hy926 cells for 30 minutes, 1, 3, 6, 12, and 24 hours, and three concentrations of VAL (i.e., 10, 1, and 0.1 mu mol/L) were used to treat EA. hy926 cells for 24 hours. The cells were divided into five groups: Control, VAL, VAL + Compound C (adenosine monophosphate-activated protein kinase [AMPK] inhibitor, 1 mu mol/L), VAL + LY294002 (Akt [protein kinase B] inhibitor, 10 mu mol/L), and VAL + L-nitro-arginine methyl ester (L-NAME, endothelial NO synthase [eNOS] inhibitor, 500 mu mol/L) groups. The NO content in the VAL-treated HUVEC line (EA. hy926) was detected using the nitrate reductase method, and western blot was used to detect the phosphorylation of Akt, AMPK, and eNOS, as well as the changes in total protein levels. VAL increased NO synthesis in EA. hy926 cells in time-and dose-dependent manners (p < 0.05) and the intracellular phosphorylation levels of Akt, AMPK, and eNOS at the corresponding time points. LY294002, Compound C, and L-NAME could inhibit the VAL-promoted NO synthesis. VAL activated Akt, AMPK, and eNOS, thus promoting NO synthesis and playing a protective role in endothelial cells. These results partially explained the mechanisms underlying the cardiovascular protective effects of VAL.
引用
收藏
页码:132 / 137
页数:6
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