Evidence map›Paper›PMID 23691105›Full record

ArticlePloS one2013

Inhibition of TNF in the brain reverses alterations in RAS components and attenuates angiotensin II-induced hypertension.

Srinivas Sriramula, Jeffrey P Cardinale, Joseph Francis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
10.9field-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

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.

  1. Pooled it
  2. Immunology of Hypertension: Pathophysiological and Therapeutic Aspects.International journal of molecular sciences · 2025
    Review
  3. Review
  4. Article
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  7. Article
  8. Article
  9. Article
  10. Article
  11. Tumor Necrosis Factor-Oxidative medicine and cellular longevity · 2022
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Review

6 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

3 authors at 1 institution in 1 country.

Srinivas SriramulaComparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, United States of America.
Jeffrey P Cardinale
Joseph Francis
Louisiana State University · US

Funding

Cytokine-induced NeurohumoralExcitation in Heart FailureR01HL080544 · NHLBI · LOUISIANA STATE UNIV A&M COL BATON ROUGE · PI FRANCIS, JOSEPH · 2005 to 2009
$1.7M
NHLBI NIH HHS HL80544NHLBI NIH HHS R01 HL080544
6 · The paper itself

Abstract

Dysfunction of brain renin-angiotensin system (RAS) components is implicated in the development of hypertension. We previously showed that angiotensin (Ang) II-induced hypertension is mediated by increased production of proinflammatory cytokines (PIC), including tumor necrosis factor (TNF), in brain cardiovascular regulatory centers such as the paraventricular nucleus (PVN). Presently, we tested the hypothesis that central TNF blockade prevents dysregulation of brain RAS components and attenuates Ang II-induced hypertension. Male Sprague-Dawley rats were implanted with radio-telemetry transmitters to measure mean arterial pressure (MAP) and subjected to intracerebroventricular (i.c.v.) infusion of etanercept (10 µg/kg/day) with/without concurrent subcutaneous 4-week Ang II (200 ng/kg/min) infusion. Chronic Ang II infusion resulted in a significant increase in MAP and cardiac hypertrophy, which was attenuated by inhibition of brain TNF with etanercept. Etanercept treatment also attenuated Ang II-induced increases in PIC and decreases in IL-10 expression in the PVN. Additionally, Ang II infusion increased expression of pro-hypertensive RAS components (ACE and AT1R), while decreasing anti-hypertensive RAS components (ACE2, Mas, and AT2 receptors), within the PVN. I.c.v. etanercept treatment reversed these changes. Ang II-infusion was associated with increased oxidative stress as indicated by increased NAD(P)H oxidase activity and super oxide production in the PVN, which was prevented by inhibition of TNF. Moreover, brain targeted TNF blockade significantly reduced Ang II-induced NOX-2 and NOX-4 mRNA and protein expression in the PVN. These findings suggest that chronic TNF blockade in the brain protects rats against Ang II-dependent hypertension and cardiac hypertrophy by restoring the balance between pro- and anti-hypertensive RAS axes and inhibiting PIC and oxidative stress genes and proteins in the PVN.

Indexed as

Angiotensin IIAnimalsBlood PressureBrainCytokinesEtanerceptHypertensionImmunoglobulin GMaleOxidative StressParaventricular Hypothalamic NucleusRatsRats, Sprague-DawleyReal-Time Polymerase Chain ReactionReceptors, Tumor Necrosis FactorRenin-Angiotensin SystemAngiotensin IICytokinesEtanerceptImmunoglobulin GReceptors, Tumor Necrosis FactorTumor Necrosis Factor-alpha

Identifiers

PMID23691105
PMCPMC3655013
OpenAlexW2042776112

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.