title: High salt medium activates RhoA/ROCK and downregulates eNOS expression via the upregulation of ADMA.
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.
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of Pediatrics, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liu
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D017673:Sodium Chloride, Dietary / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D017673:Sodium Chloride, Dietary; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein