Aldosterone-induced abnormal regulation of ENaC and SGK1 in Dahl salt-sensitive rat

Biochem Biophys Res Commun. 2006 Mar 10;341(2):376-81. doi: 10.1016/j.bbrc.2005.12.194. Epub 2006 Jan 19.

Abstract

Aldosterone plays a crucial role in controlling mineral balance in our body. The mechanism of aldosterone has been reported to elevate renal Na+ reabsorption by stimulating expression of epithelial Na+ channel (ENaC) and also activate an ENaC-regulating protein kinase, serum and glucocorticoid-regulated kinase 1 (SGK1). However, it is unknown whether aldosterone shows its stimulatory action on ENaC and SGK1 under an abnormal, salt-sensitive hypertensive condition. To clarify this point, we studied how aldosterone regulates expression of ENaC and SGK1 in Dahl salt-sensitive (DS) rat that shows hypertension with high salt diet. RNA and protein were extracted from the kidney 6 h after application of aldosterone (1.5 mg/kg body weight) subcutaneously injected into adrenalectomized DS and Dahl salt-resistant (DR) rats. Aldosterone decreased mRNA expression of beta- and gamma-ENaC in DS rat unlike DR rat, while aldosterone increased alpha-ENaC mRNA expression in DS rat similar to DR rat. Further, we found that aldosterone elevated SGK1 expression in DR rat, but not in DS rat. These observations indicate that ENaC and SGK1 are abnormally regulated by aldosterone in salt-sensitive hypertensive rats, suggesting that disturbance of the aldosterone regulation would be one of factors causing salt-sensitive hypertension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / metabolism*
  • Animals
  • Blotting, Western
  • Body Weight
  • Epithelial Sodium Channels
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression Regulation*
  • Hypertension
  • Immediate-Early Proteins / metabolism*
  • Kidney / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Models, Statistical
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Dahl
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salts / pharmacology
  • Sodium / metabolism
  • Sodium / pharmacology
  • Sodium Channels / metabolism
  • Sodium Channels / physiology*
  • Time Factors
  • Vasopressins / metabolism

Substances

  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • RNA, Messenger
  • Salts
  • Sodium Channels
  • Vasopressins
  • Aldosterone
  • RNA
  • Sodium
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3