Evidence map›Paper›PMID 25776070›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

Proinflammatory cytokines upregulate sympathoexcitatory mechanisms in the subfornical organ of the rat.

Shun-Guang Wei, Yang Yu, Zhi-Hua Zhang, Robert B Felder

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 102 citations in OpenAlex.

  1. Mechanism of paraventricular nucleus HPhysiological reports · 2026
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  4. The Gut Microbiome and Cardiac Arrhythmias.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2025
    Review
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  6. Review
  7. Article
  8. Maternal exposure to LPS results in overactivation of renal sympathetic nerve activity and hypertension in offspring rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2024
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Angiotensin II inhibits the A-type KAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2022
    Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. 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

4 authors at 1 institution in 1 country.

Shun-Guang WeiFrom the Department of Internal Medicine, University of Iowa Carver College of Medicine (S.-G.W., Y.Y., Z.-H.Z., R.B.F.) and Veterans Affairs Medical Center (R.B.F.), Iowa City, IA.
Yang YuFrom the Department of Internal Medicine, University of Iowa Carver College of Medicine (S.-G.W., Y.Y., Z.-H.Z., R.B.F.) and Veterans Affairs Medical Center (R.B.F.), Iowa City, IA.
Zhi-Hua ZhangFrom the Department of Internal Medicine, University of Iowa Carver College of Medicine (S.-G.W., Y.Y., Z.-H.Z., R.B.F.) and Veterans Affairs Medical Center (R.B.F.), Iowa City, IA.
Robert B FelderFrom the Department of Internal Medicine, University of Iowa Carver College of Medicine (S.-G.W., Y.Y., Z.-H.Z., R.B.F.) and Veterans Affairs Medical Center (R.B.F.), Iowa City, IA. robert-felder@uiowa.edu.
Veterans Health Administration · US

Funding

Cytokines and Sympathetic Activation in Heart FailureR01HL073986 · NHLBI · UNIVERSITY OF IOWA · PI FELDER, ROBERT B · 2003 to 2017
$5.2M
Brain MAP Kinases - Substrate for Sympathetic Excitation in Heart FailureR01HL096671 · NHLBI · UNIVERSITY OF IOWA · PI FELDER, ROBERT B · 2011 to 2014
$1.5M
NHLBI NIH HHS R01 HL073986NHLBI NIH HHS R01 HL096671
6 · The paper itself

Abstract

Our previous work indicated that the subfornical organ (SFO) is an important brain sensor of blood-borne proinflammatory cytokines, mediating their central effects on autonomic and cardiovascular function. However, the mechanisms by which SFO mediates the central effects of circulating proinflammatory cytokines remain unclear. We hypothesized that proinflammatory cytokines act within the SFO to upregulate the expression of excitatory and inflammatory mediators that drive sympathetic nerve activity. In urethane-anesthetized Sprague-Dawley rats, direct microinjection of tumor necrosis factor (TNF)-α (25 ng) or interleukin (IL)-1β (25 ng) into SFO increased mean blood pressure, heart rate, and renal sympathetic nerve activity within 15 to 20 minutes, mimicking the response to systemically administered proinflammatory cytokines. Pretreatment of SFO with microinjections of the angiotensin II type-1 receptor blocker losartan (1 μg), angiotensin-converting enzyme inhibitor captopril (1 μg) or cyclooxygenase-2 inhibitor NS-398 (2 μg) attenuated those responses. Four hours after the SFO microinjection of TNF-α (25 ng) or IL-1β (25 ng), mRNA for angiotensin-converting enzyme, angiotensin II type-1 receptor, TNF-α and the p55 TNF-α receptor, IL-1β and the IL-1R receptor, and cyclooxygenase-2 had increased in SFO, and mRNA for angiotensin-converting enzyme, angiotensin II type-1 receptor, and cyclooxygenase-2 had increased downstream in the hypothalamic paraventricular nucleus. Confocal immunofluorescent images revealed that immunoreactivity for the p55 TNF-α receptor and the IL-1 receptor accessory protein, a subunit of the IL-1 receptor, colocalized with angiotensin-converting enzyme, angiotensin II type-1 receptor-like, cyclooxygenase-2, and prostaglandin E2 EP3 receptor immunoreactivity in SFO neurons. These data suggest that proinflammatory cytokines act within the SFO to upregulate the expression of inflammatory and excitatory mediators that drive sympathetic excitation.

Indexed as

Up-RegulationAnimalsCytokinesDisease Models, AnimalFollow-Up StudiesHemodynamicsInflammationMaleParaventricular Hypothalamic NucleusRatsRats, Sprague-DawleySubfornical OrganSympathetic Nervous SystemTranscriptional ActivationCytokinescyclooxygenase-2cytokine receptorsparaventricular nucleussympathetic nervous system

Identifiers

PMID25776070
PMCPMC4393369
OpenAlexW2164835315

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.