Chloride homeostasis dysfunction drives hyperactivation of corticotropin-releasing factor-expressing neurons in the amygdala in stress-induced hypertension - PubMed
5 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.