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: Yu Cao, Jian-Jun Mu, Yuan Fang, Zu-Yi Yuan, Fu-Qiang Liu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 4 Pg. 8062-72 (Apr 12 2013) ISSN: 1422-0067 [Print] Switzerland
• PMID: 23584024 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• RNA, Messenger
• Sodium Chloride, Dietary
• Hydralazine
• Nitric Oxide
• N,N-dimethylarginine
• Arginine
• Nitric Oxide Synthase Type III
• Nos3 protein, rat
• PRMT1 protein, rat
• Protein-Arginine N-Methyltransferases
• Amidohydrolases
• dimethylargininase

Topics

• Amidohydrolases (genetics, metabolism)
• Animals
• Antihypertensive Agents (administration & dosage)
• Aorta (physiopathology)
• Arginine (analogs & derivatives, blood)
• Blood Pressure (drug effects, physiology)
• Hydralazine (administration & dosage)
• Hypertension (etiology, genetics, physiopathology)
• Male
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type III (genetics, metabolism)
• Protein-Arginine N-Methyltransferases (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Inbred Dahl
• Signal Transduction (drug effects)
• Sodium Chloride, Dietary (administration & dosage, adverse effects)