Evidence map›Paper›PMID 24639345›Full record

ArticleThe Journal of comparative neurology2014

Slow-pressor angiotensin II hypertension and concomitant dendritic NMDA receptor trafficking in estrogen receptor β-containing neurons of the mouse hypothalamic paraventricular nucleus are sex and age dependent.

Jose Marques-Lopes, Tracey Van Kempen, Elizabeth M Waters, Virginia M Pickel, Costantino Iadecola, Teresa A Milner

Abstract read
In one paragraph

Article in The Journal of comparative neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.0field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  6. Revisiting sex as a biological variable in hypertension research.The Journal of clinical investigation · 2024
    Review
  7. Article
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  11. Estrogen Receptor β Contributes to Both Hypertension and Hypothalamic Plasticity in a Mouse Model of Peri-Menopause.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
  12. Article
  13. RFamide-Related Peptide Neurons Modulate Reproductive Function and Stress Responses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021
    Article
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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

6 authors at 3 institutions in 1 country.

Jose Marques-LopesBrain and Mind Research Institute, Weill Cornell Medical College, New York, New York, 10065.
Tracey Van Kempen
Elizabeth M Waters
Virginia M Pickel
Costantino Iadecola
Teresa A Milner
MIND Research Institute · USCornell University · USRockefeller University · US

Funding

The Nonhuman Primate CoreP01AG016765 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI BAXTER, MARK G · 1999 to 2016
$26.1M
Radiotelemetry CoreP01HL096571 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI DAVISSON, ROBIN L · 2009 to 2013
$8.8M
ULTRASTRUCTURAL INTERACTIONS OF OPIOIDS IN HIPPOCAMPUSR01DA008259 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI MILNER, TERESA A · 1993 to 2019
$6.4M
PHARMACOLOGY AND NEUROSCIENCE OF DRUG ABUSET32DA007274 · NIDA · WEILL MEDICAL COLL OF CORNELL UNIV · PI SZETO, HAZEL H · 1991 to 2011
$4.8M
MENOPAUSAL CHANGES IN HYPOTHALAMUS AND HYPERTENSION SUSCEPTIBILITYR01HL098351 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI MILNER, TERESA A · 2011 to 2014
$1.7M
BDNF-Estrogen Interactions with Perimenopausal Mood and CognitionR21AG039850 · NIA · ROCKEFELLER UNIVERSITY · PI MILNER, TERESA A, WATERS, ELIZABETH M · 2011 to 2012
$399k
NHLBI NIH HHS HL096571NHLBI NIH HHS HL098351NHLBI NIH HHS P01 HL096571NHLBI NIH HHS R01 HL098351NIA NIH HHS AG016765NIA NIH HHS AG059850NIA NIH HHS P01 AG016765NIA NIH HHS R21 AG039850NIDA NIH HHS DA08259NIDA NIH HHS R01 DA008259NIDA NIH HHS T32 DA007274
6 · The paper itself

Abstract

The incidence of hypertension increases after menopause. Similar to humans, "slow-pressor" doses of angiotensin II (AngII) increase blood pressure in young males, but not in young female mice. However, AngII increases blood pressure in aged female mice, paralleling reproductive hormonal changes. These changes could influence receptor trafficking in central cardiovascular circuits and contribute to hypertension. Increased postsynaptic N-methyl-D-aspartate (NMDA) receptor activity in the hypothalamic paraventricular nucleus (PVN) is crucial for the sympathoexcitation driving AngII hypertension. Estrogen receptors β (ERβs) are present in PVN neurons. We tested the hypothesis that changes in ovarian hormones with age promote susceptibility to AngII hypertension, and influence NMDA receptor NR1 subunit trafficking in ERβ-containing PVN neurons. Transgenic mice expressing enhanced green fluorescent protein (EGFP) in ERβ-containing cells were implanted with osmotic minipumps delivering AngII (600 ng/kg/min) or saline for 2 weeks. AngII increased blood pressure in 2-month-old males and 18-month-old females, but not in 2-month-old females. By electron microscopy, NR1-silver-intensified immunogold (SIG) was mainly in ERβ-EGFP dendrites. At baseline, NR1-SIG density was greater in 2-month-old females than in 2-month-old males or 18-month-old females. After AngII infusion, NR1-SIG density was decreased in 2-month-old females, but increased in 2-month-old males and 18-month-old females. These findings suggest that, in young female mice, NR1 density is decreased in ERβ-PVN dendrites thus reducing NMDA receptor activity and preventing hypertension. Conversely, in young males and aged females, NR1 density is upregulated in ERβ-PVN dendrites and ultimately leads to the neurohumoral dysfunction driving hypertension.

Indexed as

AgingAngiotensin IIAnimalsBlood PressureDendritesEstrogen Receptor betaEstrous CycleFemaleGreen Fluorescent ProteinsMaleMiceMice, TransgenicNerve Tissue ProteinsNeuronsParaventricular Hypothalamic NucleusReceptors, N-Methyl-D-Aspartate2-hydroxy-4,4'-diamidinostilbene, methanesulfonate saltAngiotensin IIEstrogen Receptor betaGprin1 protein, mouseGreen Fluorescent ProteinsNerve Tissue ProteinsReceptors, N-Methyl-D-AspartateStilbamidinescardiovascularestrogenshypertensionsex differences

Identifiers

PMID24639345
PMCPMC4106979
OpenAlexW1833659243

What OpenQuestion holds

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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.