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Chloride homeostasis dysfunction drives hyperactivation of corticotropin-releasing factor-expressing neurons in the amygdala in stress-induced hypertension - PubMed

3 hours ago
  • #Neuroscience
  • #Hypertension
  • #Chloride Homeostasis
  • Stress promotes progression from borderline to sustained hypertension, mechanism unclear.
  • Study focused on CRF-expressing neurons in amygdala's central nucleus (CeA) in borderline hypertensive rats (BHRs) under chronic unpredictable mild stress (CUMS).
  • CUMS led to sustained hypertension, increased delta-FosB expression, and hyperactivation of CeA CRF neurons in BHRs.
  • Optogenetic activation of CeA CRF neurons increased sympathetic outflow and blood pressure in BHRs.
  • Impaired GABAergic inhibition, depolarized GABA reversal potential, disrupted chloride homeostasis, and increased NKCC1 expression observed in CeA CRF neurons under CUMS.
  • NKCC1 inhibition with bumetanide restored GABAergic inhibition, chloride homeostasis, normalized excitability, and reduced sympathetic tone in CUMS BHRs.
  • Findings suggest NKCC1-mediated chloride homeostasis disruption in CeA CRF neurons elevates sympathetic activity and hypertension under chronic stress.
  • Study enhances understanding of neuronal and molecular mechanisms in stress-induced hypertension, revealing potential treatment targets.