Corticotropin-releasing hormone neurons in the central nucleus of amygdala are required for chronic stress-induced hypertension.
Central nucleus of the amygdala
Chronic stress
Corticotropin-releasing hormone
Hypertension
Kv7 channel
Journal
Cardiovascular research
ISSN: 1755-3245
Titre abrégé: Cardiovasc Res
Pays: England
ID NLM: 0077427
Informations de publication
Date de publication:
06 07 2023
06 07 2023
Historique:
received:
01
05
2022
revised:
30
11
2022
accepted:
08
04
2023
pmc-release:
12
04
2024
medline:
10
7
2023
pubmed:
13
4
2023
entrez:
12
4
2023
Statut:
ppublish
Résumé
Chronic stress is a well-known risk factor for the development of hypertension. However, the underlying mechanisms remain unclear. Corticotropin-releasing hormone (CRH) neurons in the central nucleus of the amygdala (CeA) are involved in the autonomic responses to chronic stress. Here, we determined the role of CeA-CRH neurons in chronic stress-induced hypertension. Borderline hypertensive rats (BHRs) and Wistar-Kyoto (WKY) rats were subjected to chronic unpredictable stress (CUS). Firing activity and M-currents of CeA-CRH neurons were assessed, and a CRH-Cre-directed chemogenetic approach was used to suppress CeA-CRH neurons. CUS induced a sustained elevation of arterial blood pressure (ABP) and heart rate (HR) in BHRs, while in WKY rats, CUS-induced increases in ABP and HR quickly returned to baseline levels after CUS ended. CeA-CRH neurons displayed significantly higher firing activities in CUS-treated BHRs than unstressed BHRs. Selectively suppressing CeA-CRH neurons by chemogenetic approach attenuated CUS-induced hypertension and decreased elevated sympathetic outflow in CUS-treated BHRs. Also, CUS significantly decreased protein and mRNA levels of Kv7.2 and Kv7.3 channels in the CeA of BHRs. M-currents in CeA-CRH neurons were significantly decreased in CUS-treated BHRs compared with unstressed BHRs. Blocking Kv7 channel with its blocker XE-991 increased the excitability of CeA-CRH neurons in unstressed BHRs but not in CUS-treated BHRs. Microinjection of XE-991 into the CeA increased sympathetic outflow and ABP in unstressed BHRs but not in CUS-treated BHRs. CeA-CRH neurons are required for chronic stress-induced sustained hypertension. The hyperactivity of CeA-CRH neurons may be due to impaired Kv7 channel activity, which represents a new mechanism involved in chronic stress-induced hypertension.
Identifiants
pubmed: 37041718
pii: 7115384
doi: 10.1093/cvr/cvad056
pmc: PMC10325697
doi:
Substances chimiques
Corticotropin-Releasing Hormone
9015-71-8
10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1751-1762Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL139523
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL142133
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL159157
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Déclaration de conflit d'intérêts
Conflict of interest: none declared.
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