Impact of High Salt Independent of Blood Pressure on PRMT/ADMA/DDAH Pathway in the Aorta of Dahl Salt-Sensitive Rats

International Journal of Molecular Sciences

Yu Cao²  Jian-Jun Mu¹  Yuan Fang¹  Zu-Yi Yuan² 

[1] 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;

关键词: endothelial dysfunction;    asymmetric dimethylarginine;    dimethylarginine;    dimethylaminohydrolase;    endothelial nitrite oxide synthase;    oxidative stress;   

DOI  :  10.3390/ijms14048062

来源: mdpi

【 摘 要 】

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-13^BN 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland