Infusion of Valproic Acid Into the Renal Medulla Activates Stem Cell Population and Attenuates Salt-Sensitive Hypertension in Dahl S Rats

Cell Physiol Biochem. 2017;42(3):1264-1273. doi: 10.1159/000478955. Epub 2017 Jul 11.

Abstract

Background: Our previous study has detected a stem cell deficiency in the renal medulla in Dahl salt-sensitive (S) rats. This study determined whether infusion of valproic acid (VA), an agent known to stimulate the stem cell function, attenuated salt-sensitive hypertension in Dahl S rats.

Methods: Uninephrectomized Dahl S rats were infused with vehicle or VA (50mg/kg/d) into the renal medulla and fed with a low (LS) or high salt diet (HS). Stem cell marker and number were analyzed by immunohistochemistry, Real-time RT-PCR and Western blot. Sodium excretion and blood pressure were measured.

Results: VA significantly increased the mRNA and protein levels of FGF2, a stem cell niche factor, and CD133, a stem cell marker. The number of CD133+ cells was significantly increased in the renal medulla in VA-treated rats. Meanwhile, high salt-induced increases in the mRNA level of proinflammatory factors interleukin-1β and interleukin-6 were blocked in VA-treated rats. Functionally, sodium excretion in response to the blood pressure increase and acute sodium loading was significantly enhanced, sodium retention attenuated, high salt-induced increase of blood pressure reduced in VA-treated rats.

Conclusion: Activation of stem cell function by VA inhibits the activation of proinflammatory factors and attenuates salt-sensitive hypertension in Dahl S rats.

Keywords: CD133; Fibroblast growth factor-2; Inflammation; Interleukin-1β; Sodium excretion.

MeSH terms

  • AC133 Antigen / analysis
  • AC133 Antigen / metabolism
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / metabolism
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Kidney Medulla / cytology*
  • Kidney Medulla / drug effects*
  • Male
  • Rats, Inbred Dahl
  • Sodium Chloride, Dietary / metabolism
  • Stem Cells / cytology
  • Stem Cells / drug effects*
  • Valproic Acid / administration & dosage
  • Valproic Acid / pharmacology*

Substances

  • AC133 Antigen
  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Sodium Chloride, Dietary
  • Fibroblast Growth Factor 2
  • Valproic Acid