[Na +] Increases in Body Fluids Sensed by Central Na x Induce Sympathetically Mediated Blood Pressure Elevations via H +-Dependent Activation of ASIC1a

Neuron. 2019 Jan 2;101(1):60-75.e6. doi: 10.1016/j.neuron.2018.11.017. Epub 2018 Nov 29.

Abstract

Increases in sodium concentrations ([Na+]) in body fluids elevate blood pressure (BP) by enhancing sympathetic nerve activity (SNA). However, the mechanisms by which information on increased [Na+] is translated to SNA have not yet been elucidated. We herein reveal that sympathetic activation leading to BP increases is not induced by mandatory high salt intakes or the intraperitoneal/intracerebroventricular infusions of hypertonic NaCl solutions in Nax-knockout mice in contrast to wild-type mice. We identify Nax channels expressed in specific glial cells in the organum vasculosum lamina terminalis (OVLT) as the sensors detecting increases in [Na+] in body fluids and show that OVLT neurons projecting to the paraventricular nucleus (PVN) are activated via acid-sensing ion channel 1a (ASIC1a) by H+ ions exported from Nax-positive glial cells. The present results provide an insight into the neurogenic mechanisms responsible for salt-induced BP elevations.

Keywords: ASIC channel; CSF; Na(x) channel; OVLT; PVN; blood; blood pressure; body fluid; salt-sensitive hypertension; sodium concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Sensing Ion Channels / metabolism*
  • Animals
  • Blood Pressure / physiology
  • Body Fluids / chemistry
  • Body Fluids / metabolism*
  • Hypertension / metabolism*
  • Hypertension / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Optogenetics / methods
  • Organ Culture Techniques
  • Organum Vasculosum / metabolism
  • Organum Vasculosum / pathology
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Paraventricular Hypothalamic Nucleus / pathology
  • Protons
  • Random Allocation
  • Sodium / metabolism*
  • Sympathetic Nervous System / chemistry
  • Sympathetic Nervous System / metabolism
  • Voltage-Gated Sodium Channels / deficiency*

Substances

  • ASIC1 protein, mouse
  • Acid Sensing Ion Channels
  • Protons
  • Scn7a protein, mouse
  • Voltage-Gated Sodium Channels
  • Sodium