title: Impact of high salt independent of blood pressure on PRMT/ADMA/DDAH pathway in the aorta of Dahl salt-sensitive rats.
abstract: Endothelial dysfunction participates in the development and progression of salt-sensitive hypertension. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS). The objectives of this study were to investigate the impact of a high salt diet on the PRMT/ADMA/DDAH (protein arginine methyltransferases; dimethylarginine dimethylaminohydrolase) pathway in Dahl salt-sensitive (DS) rats and SS-13BN consomic (DR) rats, and to explore the mechanisms that regulate ADMA metabolism independent of blood pressure reduction. Plasma levels of nitric oxide (NO) in DS rats given a high salt diet and subjected to intragastric administration of hydralazine (SH + HYD group) were lower than those given a normal salt diet (SN group). There were significant decreases in expression and activity of dimethylarginine dimethylaminohydrolase (DDAH) and endothelial NO synthase (eNOS) in DS rats given a high diet (SH group) in comparison to the SN group. The activity of DDAH and expression of eNOS in the SH + HYD group decreased more significantly than SN group. The mRNA expression of DDAH-1 and DDAH-2 were lowest in the SH group. The results suggest that salt, independent of blood pressure, can affect the PRMT-1/ADMA/DDAH system to a certain degree and lead to endothelial dysfunction in Dahl salt-sensitive rats.
authors.affiliation: Department of Cardiovascular Medicine, First Affiliated Hospital of Medical College of Xi'an Jiaotong University, No. 277 Yanta West Road, Xi'an, Shaanxi 710061, China. mujjun@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Mu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.forename: Zu-Yi
authors.initials: ZY
authors.lastname: Yuan
authors.forename: Fu-Qiang
authors.initials: FQ
authors.lastname: Liu
mesh_terms: D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001011:Aorta / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000008:administration & dosage; D006973:Hypertension / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D015398:Signal Transduction / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000959:Antihypertensive Agents; D012333:RNA, Messenger; D017673:Sodium Chloride, Dietary; D006830:Hydralazine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase