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

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 mecha...

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Main Authors: Yingshuai Zhao, Liuyi Wang, Shanshan He, Xiaoyan Wang, Weili Shi
Format: Article
Language:English
Published: Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina 2017-05-01
Series:Bosnian Journal of Basic Medical Sciences
Subjects:
Online Access:https://bjbms.org/ojs/index.php/bjbms/article/view/1319
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spelling doaj-1bcdb34b11bb4c0a8fd012bd89a8149f2020-11-24T20:43:52ZengAssociation of Basic Medical Sciences of Federation of Bosnia and HerzegovinaBosnian Journal of Basic Medical Sciences1512-86011840-48122017-05-0117210.17305/bjbms.2017.1319145Nitric oxide synthesis-promoting effects of valsartan in human umbilical vein endothelial cells via the Akt/adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathwayYingshuai Zhao0Liuyi Wang1Shanshan He2Xiaoyan Wang3Weili Shi4Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of General Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, ChinaDepartment of General Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China; Department of General Medicine, People's Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaValsartan (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 µmol/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 µmol/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 µmol/L), VAL + LY294002 (Akt [protein kinase B] inhibitor, 10 µmol/L), and VAL + L-nitro-arginine methyl ester (L-NAME, endothelial NO synthase [eNOS] inhibitor, 500 µmol/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. https://bjbms.org/ojs/index.php/bjbms/article/view/1319Valsartannitric oxideprotein kinase Badenosine monophosphate-activated protein kinaseendothelial nitric oxide synthase
collection DOAJ
language English
format Article
sources DOAJ
author Yingshuai Zhao
Liuyi Wang
Shanshan He
Xiaoyan Wang
Weili Shi
spellingShingle Yingshuai Zhao
Liuyi Wang
Shanshan He
Xiaoyan Wang
Weili Shi
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
Bosnian Journal of Basic Medical Sciences
Valsartan
nitric oxide
protein kinase B
adenosine monophosphate-activated protein kinase
endothelial nitric oxide synthase
author_facet Yingshuai Zhao
Liuyi Wang
Shanshan He
Xiaoyan Wang
Weili Shi
author_sort Yingshuai Zhao
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina
series Bosnian Journal of Basic Medical Sciences
issn 1512-8601
1840-4812
publishDate 2017-05-01
description 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 µmol/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 µmol/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 µmol/L), VAL + LY294002 (Akt [protein kinase B] inhibitor, 10 µmol/L), and VAL + L-nitro-arginine methyl ester (L-NAME, endothelial NO synthase [eNOS] inhibitor, 500 µmol/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.
topic Valsartan
nitric oxide
protein kinase B
adenosine monophosphate-activated protein kinase
endothelial nitric oxide synthase
url https://bjbms.org/ojs/index.php/bjbms/article/view/1319
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AT xiaoyanwang nitricoxidesynthesispromotingeffectsofvalsartaninhumanumbilicalveinendothelialcellsviatheaktadenosinemonophosphateactivatedproteinkinaseendothelialnitricoxidesynthasepathway
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