Evidence map›Paper›PMID 33723600›Full record

ArticleCardiovascular research2022

Targeting angiotensin type-2 receptors located on pressor neurons in the nucleus of the solitary tract to relieve hypertension in mice.

Mazher Mohammed, Dominique N Johnson, Lei A Wang, Scott W Harden, Wanhui Sheng, Eliot A Spector, Khalid Elsaafien, Michael Bader, U Muscha Steckelings, Karen A Scott and 4 more

Open access · bronzeAbstract 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 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

22 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Vagal GABAergic signaling in autonomic control of cardiometabolic function.American journal of physiology. Cell physiology · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Alleviating Hypertension by Selectively Targeting Angiotensin Receptor-Expressing Vagal Sensory Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  17. Review
  18. Article
  19. The Angiotensin ATPharmacological reviews · 2022
    Review
  20. 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

14 authors at 3 institutions in 3 countries.

Mazher MohammedDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.ORCID 0000-0002-6728-1930
Dominique N JohnsonDepartment of Physiology and Functional Genomics, University of Florida College of Medicine, 1345 Center Drive, Room M552, Gainesville, FL 32610-0274, USA.ORCID 0000-0002-8421-043X
Lei A WangDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.
Scott W HardenDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.ORCID 0000-0002-0757-1979
Wanhui ShengDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.ORCID 0000-0001-9357-0771
Eliot A SpectorDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.ORCID 0000-0001-7891-8127
Khalid ElsaafienDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.ORCID 0000-0001-9581-918X
Michael BaderMax-Delbrück Center for Molecular Medicine (MDC), Robert-Rössle-Str. 10, 13125 Berlin-Buch, Germany.
U Muscha SteckelingsDepartment of Cardiovascular & Renal Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløws Vej 21-25, Odense C - DK-5000, Denmark.
Karen A ScottDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.
Charles J FrazierDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.ORCID 0000-0003-3550-4789
Colin SumnersDepartment of Physiology and Functional Genomics, University of Florida College of Medicine, 1345 Center Drive, Room M552, Gainesville, FL 32610-0274, USA.ORCID 0000-0002-9689-2255
Eric G KrauseDepartment of Pharmacodynamics, University of Florida College of Pharmacy, 1345 Center Dr. JHMHC Room P1-20, Gainesville, FL 32610, USA.
Annette D de KloetDepartment of Physiology and Functional Genomics, University of Florida College of Medicine, 1345 Center Drive, Room M552, Gainesville, FL 32610-0274, USA.
University of Florida · USMax Delbrück Center · DEUniversity of Southern Denmark · DK

Funding

Interrogating stress-relieving neural circuits to alleviate cardiovascular diseaseR35HL150750 · NHLBI · UNIVERSITY OF FLORIDA · PI Eric Gerald Krause · 2020 to 2026
$5.9M
Neurons expressing angiotensin type 2 receptors in the NTS as an access point for cardiovascular control.R01HL136595 · NHLBI · UNIVERSITY OF FLORIDA · PI COLIN SUMNERS, Annette Diane de Kloet · 2018 to 2026
$4.8M
Paraventricular nucleus regulatory mechanisms in stress and hypertensionR01HL093186 · NHLBI · UNIVERSITY OF FLORIDA · PI SCHEUER, DEBORAH A, SUMNERS, COLIN · 2009 to 2013
$2.0M
Interrogating distinct angiotensin type-1 and type-2 receptor containing brain circuits to understand and alleviate hypertensionR01HL145028 · NHLBI · UNIVERSITY OF FLORIDA · PI DE KLOET, ANNETTE DIANE · 2019 to 2023
$1.9M
Central Mechanisms Underlying the Stress Dampening Effects of Acute HypernatremiaR01HL122494 · NHLBI · UNIVERSITY OF FLORIDA · PI KRAUSE, ERIC GERALD · 2015 to 2019
$1.9M
Novel role of central AT2R in blood pressure regulationR00HL125805 · NHLBI · UNIVERSITY OF FLORIDA · PI DE KLOET, ANNETTE DIANE · 2016 to 2018
$746k
Central Angiotensin receptors and teh neural control of homeostasisR00HL096830 · NHLBI · UNIVERSITY OF FLORIDA · PI KRAUSE, ERIC GERALD · 2011 to 2013
$727k
Central AT1 receptors and the integrated stress response.K99HL096830 · NHLBI · UNIVERSITY OF CINCINNATI · PI KRAUSE, ERIC GERALD · 2009 to 2010
$248k
Novel role of central AT2R in blood pressure regulationK99HL125805 · NHLBI · UNIVERSITY OF FLORIDA · PI DE KLOET, ANNETTE DIANE · 2015 to 2016
$225k
NHLBI NIH HHS K99 HL096830NHLBI NIH HHS K99 HL125805NHLBI NIH HHS R00 HL096830NHLBI NIH HHS R00 HL125805NHLBI NIH HHS R01 HL093186NHLBI NIH HHS R01 HL122494NHLBI NIH HHS R01 HL136595NHLBI NIH HHS R01 HL145028NHLBI NIH HHS R35 HL150750
6 · The paper itself

Abstract

aimsThese studies evaluate whether angiotensin type-2 receptors (AT2Rs) that are expressed on γ-aminobutyric acid (GABA) neurons in the nucleus of the solitary tract (NTS) represent a novel endogenous blood pressure-lowering mechanism. METHODS AND

resultsExperiments combined advanced genetic and neuroanatomical techniques, pharmacology, electrophysiology, and optogenetics in mice to define the structure and cardiovascular-related function of NTS neurons that contain AT2R. Using mice with Cre-recombinase directed to the AT2R gene, we discovered that optogenetic stimulation of AT2R-expressing neurons in the NTS increases GABA release and blood pressure. To evaluate the role of the receptor, per se, in cardiovascular regulation, we chronically delivered C21, a selective AT2R agonist, into the brains of normotensive mice and found that central AT2R activation reduces GABA-related gene expression and blunts the pressor responses induced by optogenetic excitation of NTS AT2R neurons. Next, using in situ hybridization, we found that the levels of Agtr2 mRNAs in GABAergic NTS neurons rise during experimentally induced hypertension, and we hypothesized that this increased expression may be exploited to ameliorate the disease. Consistent with this, final experiments revealed that central administration of C21 attenuates hypertension, an effect that is abolished in mice lacking AT2R in GABAergic NTS neurons.

conclusionThese studies unveil novel hindbrain circuits that maintain arterial blood pressure, and reveal a specific population of AT2R that can be engaged to alleviate hypertension. The implication is that these discrete receptors may serve as an access point for activating an endogenous depressor circuit.

Indexed as

HypertensionSolitary NucleusAnimalsImidazolesMiceNeuronsReceptor, Angiotensin, Type 2SulfonamidesThiophenescompound 21ImidazolesReceptor, Angiotensin, Type 2SulfonamidesThiophenesBaroreflexBlood pressureGABAHindbrainRAS

Identifiers

PMID33723600
PMCPMC9020199
OpenAlexW3139410911

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.