Evidence map›Paper›PMID 33512443›Full record

ArticleCardiovascular research2022

Impaired Kv7 channel activity in the central amygdala contributes to elevated sympathetic outflow in hypertension.

Zhao-Fu Sheng, Hua Zhang, PeiRu Zheng, Shanyan Chen, Zezong Gu, Jing-Jing Zhou, Jeffery G Phaup, Hui-Ming Chang, Edward T H Yeh, Hui-Lin Pan and 1 more

Open access · greenAbstract read
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  3. Evaluation of Small-Molecule Candidates as Modulators of M-Type KInternational journal of molecular sciences · 2025
    Review
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  8. Article
  9. Hypothalamic Corticotropin-Releasing Hormone Contributes to Hypertension in Spontaneously Hypertensive Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Evidence for Dual Activation ofInternational journal of molecular sciences · 2022
    Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Zhao-Fu ShengCenter for Precision Medicine, Department of Medicine, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.
Hua ZhangCenter for Precision Medicine, Department of Medicine, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.ORCID 0000-0002-5532-1659
PeiRu ZhengCenter for Precision Medicine, Department of Medicine, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.
Shanyan ChenDepartment of Pathology and Anatomical Sciences, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.ORCID 0000-0003-3980-5749
Zezong GuDepartment of Pathology and Anatomical Sciences, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.
Jing-Jing ZhouDepartment of Anesthesiology and Perioperative Medicine, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Jeffery G PhaupCenter for Precision Medicine, Department of Medicine, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.
Hui-Ming ChangDepartments of Pharmacology and Toxicology and Internal Medicine, The University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205, USA.ORCID 0000-0002-5856-3397
Edward T H YehDepartments of Pharmacology and Toxicology and Internal Medicine, The University of Arkansas for Medical Sciences, 4301 West Markham St., Little Rock, AR 72205, USA.ORCID 0000-0001-8184-7294
Hui-Lin PanDepartment of Anesthesiology and Perioperative Medicine, The University of Texas, MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
De-Pei LiCenter for Precision Medicine, Department of Medicine, School of Medicine, University of Missouri, 1 Hospital Drive, Columbia, MO 65212, USA.ORCID 0000-0003-1478-3854
University of Missouri Hospital · USThe University of Texas MD Anderson Cancer Center · USUniversity of Arkansas for Medical Sciences · US

Funding

Neural Mechanisms of Calcineurin Inhibitor-Induced HypertensionR01HL154512 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI PAN, HUI-LIN · 2020 to 2023
$2.3M
Mechanisms of Stress-Induced HypertensionR01HL139523 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LI, DE-PEI, PAN, HUI-LIN · 2018 to 2021
$1.8M
Synaptic Mechanisms of Stress-Induced HypertensionR01HL142133 · NHLBI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LI, DE-PEI, PAN, HUI-LIN · 2018 to 2021
$1.8M
NHLBI NIH HHS R01 HL139523NHLBI NIH HHS R01 HL142133
6 · The paper itself

Abstract

aimsElevated sympathetic outflow is associated with primary hypertension. However, the mechanisms involved in heightened sympathetic outflow in hypertension are unclear. The central amygdala (CeA) regulates autonomic components of emotions through projections to the brainstem. The neuronal Kv7 channel is a non-inactivating voltage-dependent K+ channel encoded by KCNQ2/3 genes involved in stabilizing the neuronal membrane potential and regulating neuronal excitability. In this study, we investigated if altered Kv7 channel activity in the CeA contributes to heightened sympathetic outflow in hypertension. METHODS AND

resultsThe mRNA and protein expression levels of Kv7.2/Kv7.3 in the CeA were significantly reduced in spontaneously hypertensive rats (SHRs) compared with Wistar-Kyoto (WKY) rats. Lowering blood pressure with coeliac ganglionectomy in SHRs did not alter Kv7.2 and Kv7.3 channel expression levels in the CeA. Fluospheres were injected into the rostral ventrolateral medulla (RVLM) to retrogradely label CeA neurons projecting to the RVLM (CeA-RVLM neurons). Kv7 channel currents recorded from CeA-RVLM neurons in brain slices were much smaller in SHRs than in WKY rats. Furthermore, the basal firing activity of CeA-RVLM neurons was significantly greater in SHRs than in WKY rats. Bath application of specific Kv7 channel blocker 10, 10-bis (4-pyridinylmethyl)-9(10H)-anthracnose (XE-991) increased the excitability of CeA-RVLM neurons in WKY rats, but not in SHRs. Microinjection of XE-991 into the CeA increased arterial blood pressure (ABP) and renal sympathetic nerve activity (RSNA), while microinjection of Kv7 channel opener QO-58 decreased ABP and RSNA, in anaesthetized WKY rats but not SHRs.

conclusionsOur findings suggest that diminished Kv7 channel activity in the CeA contributes to elevated sympathetic outflow in primary hypertension. This novel information provides new mechanistic insight into the pathogenesis of neurogenic hypertension.

Indexed as

Arterial PressureAnimalsCentral Amygdaloid NucleusDisease Models, AnimalHypertensionKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelLuminescent ProteinsMaleMedulla OblongataMembrane PotentialsMiceMice, Inbred C57BLMice, TransgenicNeuroanatomical Tract-Tracing TechniquesNeuronsKCNQ2 Potassium ChannelKcnq2 protein, ratKCNQ3 Potassium ChannelKcnq3 protein, ratLuminescent ProteinsPotassiumRed Fluorescent ProteinVesicular Glutamate Transport Protein 2Autonomic nervous systemCentral amygdalaHypertensionPotassium channelSympathetic nervous system

Identifiers

PMID33512443
PMCPMC8803073
OpenAlexW3122013308

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.