Evidence map›Paper›PMID 25427952›Full record

ArticleBrain structure & function2016

Reporter mouse strain provides a novel look at angiotensin type-2 receptor distribution in the central nervous system.

Annette D de Kloet, Lei Wang, Jacob A Ludin, Justin A Smith, David J Pioquinto, Helmut Hiller, U Muscha Steckelings, Deborah A Scheuer, Colin Sumners, Eric G Krause

Abstract read
In one paragraph

Article in Brain structure & function, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

69 citing papers in PubMed, 99 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. 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
  6. Article
  7. The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  8. The ATMolecules (Basel, Switzerland) · 2023
    Review
  9. Angiotensin Type 2 Receptor Pharmacological Agonist Relieves Neurocognitive Deficits via Reducing Neuroinflammation and Microglial Engulfment of Dendritic Spines.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023
    Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. The Angiotensin ATPharmacological reviews · 2022
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 2 countries.

Annette D de KloetDepartment of Physiology and Functional Genomics, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Drive (Bldg. 59, RM L4-162), Gainesville, FL, 32611, USA. adekloet@ufl.edu.
Lei WangDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, 32611, USA.
Jacob A LudinDepartment of Physiology and Functional Genomics, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Drive (Bldg. 59, RM L4-162), Gainesville, FL, 32611, USA.
Justin A SmithDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, 32611, USA.
David J PioquintoDepartment of Physiology and Functional Genomics, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Drive (Bldg. 59, RM L4-162), Gainesville, FL, 32611, USA.
Helmut HillerDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, 32611, USA.
U Muscha SteckelingsDepartment of Cardiovascular and Renal Research, University of Southern Denmark, Odense C, Denmark.
Deborah A ScheuerDepartment of Physiology and Functional Genomics, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Drive (Bldg. 59, RM L4-162), Gainesville, FL, 32611, USA.
Colin SumnersDepartment of Physiology and Functional Genomics, College of Medicine, McKnight Brain Institute, University of Florida, 100 S. Newell Drive (Bldg. 59, RM L4-162), Gainesville, FL, 32611, USA.
Eric G KrauseDepartment of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville, 32611, USA.
University of Florida · USUniversity of Southern Denmark · DK

Funding

MIF: A novel CNS regulator of cardiovascular functionR01HL076803 · NHLBI · UNIVERSITY OF FLORIDA · PI SUMNERS, COLIN · 2005 to 2014
$4.0M
Multidisciplinary Training Program in HypertensionT32HL083810 · NHLBI · UNIVERSITY OF FLORIDA · PI WOOD, CHARLES E · 2007 to 2017
$2.5M
Paraventricular nucleus regulatory mechanisms in stress and hypertensionR01HL093186 · NHLBI · UNIVERSITY OF FLORIDA · PI SCHEUER, DEBORAH A, SUMNERS, COLIN · 2009 to 2013
$2.0M
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
Angiotensin-II, Hypothalamic Inflammation and Neurogenic HypertensionF32HL116074 · NHLBI · UNIVERSITY OF FLORIDA · PI DE KLOET, ANNETTE DIANE · 2012 to 2014
$91k
NHLBI NIH HHS F32 HL116074NHLBI NIH HHS F32-HL-116074NHLBI NIH HHS HL-076803NHLBI NIH HHS HL-093186NHLBI NIH HHS HL-096830NHLBI NIH HHS K99 HL096830NHLBI NIH HHS K99 HL125805NHLBI NIH HHS R00 HL096830NHLBI NIH HHS R00 HL125805NHLBI NIH HHS R01 HL076803NHLBI NIH HHS R01 HL093186NHLBI NIH HHS R01 HL122494NHLBI NIH HHS T32 HL083810NHLBI NIH HHS T32-HL-083810
6 · The paper itself

Abstract

Angiotensin-II acts at its type-1 receptor (AT1R) in the brain to regulate body fluid homeostasis, sympathetic outflow and blood pressure. However, the role of the angiotensin type-2 receptor (AT2R) in the neural control of these processes has received far less attention, largely because of limited ability to effectively localize these receptors at a cellular level in the brain. The present studies combine the use of a bacterial artificial chromosome transgenic AT2R-enhanced green fluorescent protein (eGFP) reporter mouse with recent advances in in situ hybridization (ISH) to circumvent this obstacle. Dual immunohistochemistry (IHC)/ISH studies conducted in AT2R-eGFP reporter mice found that eGFP and AT2R mRNA were highly co-localized within the brain. Qualitative analysis of eGFP immunoreactivity in the brain then revealed localization to neurons within nuclei that regulate blood pressure, metabolism, and fluid balance (e.g., NTS and median preoptic nucleus [MnPO]), as well as limbic and cortical areas known to impact stress responding and mood. Subsequently, dual IHC/ISH studies uncovered the phenotype of specific populations of AT2R-eGFP cells. For example, within the NTS, AT2R-eGFP neurons primarily express glutamic acid decarboxylase-1 (80.3 ± 2.8 %), while a smaller subset express vesicular glutamate transporter-2 (18.2 ± 2.9 %) or AT1R (8.7 ± 1.0 %). No co-localization was observed with tyrosine hydroxylase in the NTS. Although AT2R-eGFP neurons were not observed within the paraventricular nucleus (PVN) of the hypothalamus, eGFP immunoreactivity is localized to efferents terminating in the PVN and within GABAergic neurons surrounding this nucleus. These studies demonstrate that central AT2R are positioned to regulate blood pressure, metabolism, and stress responses.

Indexed as

AnimalsBrainCentral Nervous SystemGABAergic NeuronsHypothalamusImmunohistochemistryMaleMiceMice, TransgenicModels, AnimalParaventricular Hypothalamic NucleusPreoptic AreaReceptor, Angiotensin, Type 2RNA, MessengerTyrosine 3-MonooxygenaseVesicular Glutamate Transport Protein 2Receptor, Angiotensin, Type 2RNA, MessengerTyrosine 3-MonooxygenaseVesicular Glutamate Transport Protein 2AT2Blood pressureBrainHypertensionRenin

Identifiers

PMID25427952
PMCPMC4446257
OpenAlexW1969442403

What OpenQuestion holds

Textmetadata
LicenceTDM
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.