Impact of high salt independent of blood pressure on PRMT/ADMA/DDAH pathway in the aorta of Dahl salt-sensitive rats

Int J Mol Sci. 2013 Apr 12;14(4):8062-72. doi: 10.3390/ijms14048062.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • 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