High salt medium activates RhoA/ROCK and downregulates eNOS expression via the upregulation of ADMA

Cao,Yu; Fang,Yuan; Mu,Jianjun; Liu,Xiaohong

doi:10.3892/mmr.2016.5241

High salt medium activates RhoA/ROCK and downregulates eNOS expression via the upregulation of ADMA

Authors:
- Yu Cao
- Yuan Fang
- Jianjun Mu
- Xiaohong Liu
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Affiliations: Department of Pediatrics, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: May 11, 2016 https://doi.org/10.3892/mmr.2016.5241
Pages: 606-612

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Abstract

Endothelial dysfunction has an important role in the development and progression of salt-sensitive hypertension. Asymmetric dimethylarginine (ADMA), which is an endogenous inhibitor of nitric oxide synthase (NOS), has been demonstrated to be involved in the pathophysiological processes of endothelial dysfunction and salt‑sensitive hypertension. However, it is currently unclear how high salt intake may induce these processes. The present study investigated the effects of high salt medium on ADMA, endothelial NOS (eNOS) and the Ras homolog gene family, member A (RhoA)/Rho-associated protein kinase (ROCK) pathway in the EA.hy926 umbilical vein cell line. The results demonstrated that high salt medium significantly increased the concentration of ADMA, the expression of protein arginine methyltransferase 1 (PRMT‑1) and RhoA, and the activity of ROCK, and downregulated the expression of eNOS. Knockdown of PRMT-1 with small interfering RNA (siRNA) significantly abrogated the aforementioned effects. These results indicated that ADMA has a key role in high salt‑mediated activation of the RhoA/ROCK pathway and inhibition of eNOS biosynthesis. siRNA‑PRMT‑1 may be considered a novel remedy for the treatment of endothelial dysfunction.

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