Evidence map›Paper›PMID 27698069›Full record

ArticleHypertension (Dallas, Tex. : 1979)2016

Astrocytes Contribute to Angiotensin II Stimulation of Hypothalamic Neuronal Activity and Sympathetic Outflow.

Javier E Stern, Sookjin Son, Vinicia C Biancardi, Hong Zheng, Neeru Sharma, Kaushik P Patel

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
15.0field-weighted citation impact, top 1% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.

  1. Pooled it
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  12. Neuroimmunology of Cardiovascular Disease.Current hypertension reports · 2024
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1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Javier E SternFrom the Department of Physiology, Augusta University, GA (J.E.S., S.S., V.C.B.); and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (H.Z., N.S., K.P.P.). jstern@augusta.edu.
Sookjin SonFrom the Department of Physiology, Augusta University, GA (J.E.S., S.S., V.C.B.); and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (H.Z., N.S., K.P.P.).
Vinicia C BiancardiFrom the Department of Physiology, Augusta University, GA (J.E.S., S.S., V.C.B.); and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (H.Z., N.S., K.P.P.).
Hong ZhengFrom the Department of Physiology, Augusta University, GA (J.E.S., S.S., V.C.B.); and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (H.Z., N.S., K.P.P.).
Neeru SharmaFrom the Department of Physiology, Augusta University, GA (J.E.S., S.S., V.C.B.); and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (H.Z., N.S., K.P.P.).
Kaushik P PatelFrom the Department of Physiology, Augusta University, GA (J.E.S., S.S., V.C.B.); and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (H.Z., N.S., K.P.P.).
Augusta University · US

Funding

The Role of Excitatory Input into the PVN on Increased Sympathetic Drive in HeartP01HL062222 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SCHULTZ, HAROLD D · 1999 to 2019
$32.2M
Research Pilot Project ProgramP30GM106397 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI JOHNSON, KEITH R · 2013 to 2017
$4.9M
Altered CNS Intercellular Signaling Mechanisms in Cardiovascular DiseaseR01HL090948 · NHLBI · UNIVERSITY OF CINCINNATI · PI STERN, JAVIER E · 2008 to 2017
$3.0M
CENTRAL NEURONAL-GLIAL MECHANISMS AND NEUROHUMORAL ACTIVATION IN HYPERTENSIONR01HL112225 · NHLBI · GEORGIA STATE UNIVERSITY · PI STERN, JAVIER E · 2012 to 2015
$1.5M
Role of HIF1-alpha and Renal afferents in Activation of the PVN in Heart FailureR56HL124104 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PATEL, KAUSHIK P · 2014 to 2014
$354k
NHLBI NIH HHS P01 HL062222NHLBI NIH HHS R01 HL090948NHLBI NIH HHS R01 HL112225NHLBI NIH HHS R56 HL124104NIGMS NIH HHS P30 GM106397
6 · The paper itself

Abstract

Angiotensin II (AngII) is a key neuropeptide that acting within the brain hypothalamic paraventricular nucleus regulates neurohumoral outflow to the circulation. Moreover, an exacerbated AngII action within the paraventricular nucleus contributes to neurohumoral activation in hypertension. Although AngII effects involve changes in paraventricular nucleus neuronal activity, the precise underlying mechanisms, cellular targets, and distribution of AngII receptors within the paraventricular nucleus remain largely unknown. Thus, whether AngII effects involve direct actions on paraventricular neurons, or whether it acts via intermediary cells, such as astrocytes, is still controversial. To address this important gap in our knowledge, we used a multidisciplinary approach combining patch-clamp electrophysiology in presympathetic paraventricular neurons and astrocytes, along with in vivo sympathetic nerve recordings and astrocyte-targeted gene manipulations. We present evidence for a novel mechanism underlying central AngII actions, which involves astrocytes as major intermediary cellular targets. We found that AngII type 1 receptor mRNA is expressed in paraventricular astrocytes. Moreover, we report that AngII inhibited glutamate transporter function, increasing in turn extracellular glutamate levels. This resulted in the activation of neuronal extrasynaptic NMDA (N-methyl-d-aspartate) receptors, increased presympathetic neuronal activity, enhanced sympathoexcitatory outflow, and increased blood pressure. Together, our studies support astrocytes as critical intermediary cell types mediating brain AngII regulation of the circulation and indicate that AngII-mediated neuronal and sympathoexcitatory effects are dependent on a unique neuroglial signaling modality involving nonsynaptic glutamate transmission.

Indexed as

Angiotensin IIAnimalsAstrocytesBlotting, WesternCells, CulturedElectrophysiologyGlutamic AcidHypertensionMaleNeuronsParaventricular Hypothalamic NucleusRatsSympathetic Nervous SystemAngiotensin IIGlutamic Acidangiotensinastrocyteblood pressureheart failurehypothalamus

Identifiers

PMID27698069
PMCPMC5159229
OpenAlexW2529817782

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.