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

Authors

  • Yingshuai Zhao Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of General Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China
  • Liuyi Wang Department of General Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China; Department of General Medicine, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Shanshan He Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Xiaoyan Wang Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
  • Weili Shi Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China

DOI:

https://doi.org/10.17305/bjbms.2017.1319

Keywords:

Valsartan, nitric oxide, protein kinase B, adenosine monophosphate-activated protein kinase, endothelial nitric oxide synthase

Abstract

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.

Author Biographies

  • Yingshuai Zhao, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of General Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China

    Department of Cardiology;

    Department of General Medicine

  • Liuyi Wang, Department of General Medicine, Henan Provincial People’s Hospital, Zhengzhou, Henan, China; Department of General Medicine, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Department of General Medicine

  • Shanshan He, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
    Department of Cardiology
  • Xiaoyan Wang, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
    Department of Cardiology
  • Weili Shi, Department of Cardiology, People’s Hospital of Zhengzhou University, Zhengzhou, Henan, China
    Department of Cardiology

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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

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Published

20-05-2017

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Translational and Clinical Research

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1.
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. Biomol Biomed [Internet]. 2017 May 20 [cited 2024 Mar. 29];17(2):132-7. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/1319