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.
Highlights
Endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases and participates in the development and progression of salt-sensitive hypertension [1]
The results suggest that salt, independent of blood pressure, can affect the protein arginine methyltransferases (PRMTs)-1/Asymmetric dimethylarginine (ADMA)/dimethylarginine dimethylaminohydrolase (DDAH) system to a certain degree and lead to endothelial dysfunction in Dahl salt-sensitive rats
There are two broad types of PRMTs: PRMT-1 catalyze the formation of ADMA, whereas PRMT-2 methylate both of the guanidino nitrogens and result in the formation of symmetric dimethylarginine (SDMA); SDMA has no inhibitory activity [8,9]
Summary
Endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases and participates in the development and progression of salt-sensitive hypertension [1]. Nitric oxide (NO) plays an important role in the regulation of vasodilatation [2,3]. One important molecular mechanism is an endogenous competitive inhibitor of nitric oxide synthase (NOS), NG,NG-dimethylarginine (asymmetrical dimethylarginine, ADMA) [4]. A growing body of evidence suggests that ADMA is an independent risk factor in the pathophysiology of salt-sensitive hypertension [5,6,7]. ADMA is synthesized endogenously during the methylation of protein arginine residues by protein arginine methyltransferases (PRMTs). There are two broad types of PRMTs: PRMT-1 catalyze the formation of ADMA, whereas PRMT-2 methylate both of the guanidino nitrogens and result in the formation of symmetric dimethylarginine (SDMA); SDMA has no inhibitory activity [8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
