Journal article
Corticotropin-releasing hormone neurons in the central nucleus of amygdala are required for chronic stress-induced hypertension
Cardiovascular research, Vol.119(8), pp.1751-1762
06/2023
DOI: 10.1093/cvr/cvad056
PMCID: PMC10325697
PMID: 37041718
Abstract
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.
We found that hyperactivity of CRH neurons in the CeA, likely due to diminished Kv7 channel activity, play a major role in the development of chronic stress-induced hypertension. Our study suggests that CRH neurons in the brain may be targeted for treating chronic stress-induced hypertension. Thus, increasing Kv7 channel activity or overexpressing Kv7 channels in the CeA may reduce stress-induced hypertension. Further studies are needed to delineate how chronic stress diminishes Kv7 channel activity in the brain.
Details
- Title: Subtitle
- Corticotropin-releasing hormone neurons in the central nucleus of amygdala are required for chronic stress-induced hypertension
- Creators
- Zhao-Fu Sheng - University of MissouriHua Zhang - University of MissouriJeffery G Phaup - University of MissouriPeiRu Zheng - University of MissouriXunLei Kang - University of MissouriZhenguo Liu - University of MissouriHui-Ming Chang - University of Arkansas for Medical SciencesEdward T H Yeh - University of Arkansas for Medical SciencesAlan Kim Johnson - University of IowaHui-Lin Pan - The University of Texas MD Anderson Cancer CenterDe-Pei Li - University of Missouri
- Resource Type
- Journal article
- Publication Details
- Cardiovascular research, Vol.119(8), pp.1751-1762
- DOI
- 10.1093/cvr/cvad056
- PMID
- 37041718
- PMCID
- PMC10325697
- eISSN
- 1755-3245
- Grant note
- DOI: 10.13039/100000050, name: National Heart, Lung, and Blood Institute, award: HL142133, HL139523, HL159157
- Language
- English
- Electronic publication date
- 04/12/2023
- Date published
- 06/2023
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health and Human Physiology
- Record Identifier
- 9984388753802771
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