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Activation of Corticotropin‐Releasing Hormone Neurons in the Central Nucleus of Amygdala is required for Chronic Stress‐Induced Hypertension
Author(s) -
Sheng ZhaoFu,
Zhang Hua,
Phaup Jeffery,
Zheng PeiRu,
Pan HuiLin,
Li DePei
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02013
Subject(s) - amygdala , stress hormone , corticotropin releasing hormone , nucleus , hormone , central nucleus of the amygdala , neuroscience , medicine , endocrinology , psychology
Background Chronic stress is a well‐known risk factor for the etiology of hypertension. However, the underlying neural mechanisms remain largely unknown. Corticotropin‐releasing hormone (CRH) neuroendocrine cells in central nucleus of the amygdala (CeA) are critical in mediating autonomic response to chronic stress. Therefore, we determined the role of CeA‐CRH neurons in hypertension induced by chronic stress. Methods Broadline hypertensive rats (BHRs) were subjected to chronic unpredictable stress (CUS). Identified CeA‐CRH neuron firing activity and M‐currents were recorded by whole‐cell patch‐clamp technique in brain slice preparation. A CRH‐Cre‐directed chemogenetic approach was used to suppress CeA‐CRH neurons. Kv7 channel protein and mRNA level were determined by western‐blot and quantitative RT‐PCR methods, respectively. Results CUS treatment induced a sustained elevation of blood pressure in BHRs and a significant increase in c‐Fos expression CeA‐CRH neurons. Identified CeA‐CRH neurons displayed significantly higher spontaneous firing activities in BHRs subjected to CUS than in unstressed BHRs. Specifically suppressing CeA‐CRH neurons activity by using CRH‐Cre‐directed chemogenetic approach restrained CUS‐induced sustained hypertension in BHRs. Both mRNA and protein levels of Kv7.2 and Kv7.3 channels were decreased in CeA of BHRs subjected to CUS. M‐currents recorded from CeA‐CRH neurons were significantly decreased in CUS BHRs compared with unstressed BHRs. Blocking Kv7 channel with its specific antagonist increased excitability of CeA‐CRH neurons in unstressed BHRs whereas did not alter their excitability in BHRs subjected to CUS. Conclusions These data suggest that CeA‐CRH neurons are required for the development of chronic stress‐induced hypertension. The hyperactivity of CeA‐CRH neurons is due to impaired Kv7 channel activity induced by chronic stress. These findings revealed a novel mechanism involved in chronic stress‐induced hypertension.