Evidence map›Paper›PMID 36448464›Full record

ArticleHypertension (Dallas, Tex. : 1979)2023

Amount of Pannexin 1 in Smooth Muscle Cells Regulates Sympathetic Nerve-Induced Vasoconstriction.

Luke S Dunaway, Marie Billaud, Edgar Macal, Miranda E Good, Christopher B Medina, Ulrike Lorenz, Kodi Ravichandran, Michael Koval, Brant E Isakson

Open access · bronzeAbstract read
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Pannexins in the vasculature.American journal of physiology. Heart and circulatory physiology · 2025
    Review
  4. Pannexin channels in the kidney.American journal of physiology. Renal physiology · 2025
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
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

9 authors at 5 institutions in 1 country.

Luke S DunawayRobert M. Berne Cardiovascular Research Center (L.S.D., E.M., B.E.I.), University of Virginia School of Medicine, Charlottesville.
Marie BillaudDepartment of Surgery, Division of Thoracic and Cardiac Surgery, Brigham and Women's Hospital, Boston MA (M.B.).ORCID 0000-0002-7591-0362
Edgar MacalRobert M. Berne Cardiovascular Research Center (L.S.D., E.M., B.E.I.), University of Virginia School of Medicine, Charlottesville.
Miranda E GoodMolecular Cardiology Research Institute, Tufts Medical Center, Boston, MA (M.E.G.).ORCID 0000-0001-7775-1863
Christopher B MedinaCenter for Cell Clearance (C.B.M.), University of Virginia School of Medicine, Charlottesville.
Ulrike LorenzDepartment of Microbiology, Immunology and Cancer Biology (C.B.M., U.L.), University of Virginia School of Medicine, Charlottesville.
Kodi RavichandranCarter Immunology Center (U.L., K.R.), University of Virginia School of Medicine, Charlottesville.
Michael KovalDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine (M.K.), Emory University School of Medicine, Atlanta, GA.ORCID 0000-0002-5422-5614
Brant E IsaksonRobert M. Berne Cardiovascular Research Center (L.S.D., E.M., B.E.I.), University of Virginia School of Medicine, Charlottesville.ORCID 0000-0002-7692-6294
University of Virginia · USCarter Center · USBrigham and Women's Hospital · USEmory University · USTufts Medical Center · US

Funding

Role of Pannexins in Vascular Smooth Muscle CellsP01HL120840 · NHLBI · UNIVERSITY OF VIRGINIA · PI ISAKSON, BRANT E · 2014 to 2023
$24.0M
BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Purinergic Regulation of Veinous Endothelial PermeabilityR01HL137112 · NHLBI · UNIVERSITY OF VIRGINIA · PI Brant E Isakson, MICHAEL H. KOVAL · 2018 to 2026
$4.7M
Defining SMC phenotypes critical in late stage atherosclerosis pathogenesisR01HL136314 · NHLBI · UNIVERSITY OF VIRGINIA · PI OWENS, GARY K · 2018 to 2021
$3.0M
Vascular Pannexin 1 in Ischemic StrokeR00HL143165 · NHLBI · TUFTS MEDICAL CENTER · PI GOOD, MIRANDA E · 2020 to 2022
$747k
Vascular Pannexin 1 in Ischemic StrokeK99HL143165 · NHLBI · UNIVERSITY OF VIRGINIA · PI GOOD, MIRANDA E · 2018 to 2019
$206k
Pannexin 1 Channels in Cerebral Arterial Myogenic RegulationF32HL131399 · NHLBI · UNIVERSITY OF VIRGINIA · PI GOOD, MIRANDA E · 2016 to 2017
$71k
NHLBI NIH HHS F32 HL131399NHLBI NIH HHS K99 HL143165NHLBI NIH HHS P01 HL120840NHLBI NIH HHS R00 HL143165NHLBI NIH HHS R01 HL136314NHLBI NIH HHS R01 HL137112NHLBI NIH HHS T32 HL007284
6 · The paper itself

Abstract

backgroundPanx1 (pannexin 1) forms high conductance channels that secrete ATP upon stimulation. The role of Panx1 in mediating constriction in response to direct sympathetic nerve stimulation is not known. Additionally, it is unknown how the expression level of Panx1 in smooth muscle cells (SMCs) influences α-adrenergic responses. We hypothesized that the amount of Panx1 in SMCs dictates the levels of sympathetic constriction and blood pressure.

methodsTo test this hypothesis, we used genetically modified mouse models enabling expression of Panx1 in vascular cells to be varied. Electrical field stimulation on isolated arteries and blood pressure were assessed.

resultsGenetic deletion of SMC Panx1 prevented constriction by electric field stimulation of sympathetic nerves. Conversely, overexpression of Panx1 in SMCs using a ROSA26 transgenic model increased sympathetic nerve-mediated constriction. Connexin 43 hemichannel inhibitors did not alter constriction. Next, we evaluated the effects of altered SMC Panx1 expression on blood pressure. To do this, we created mice combining a global Panx1 deletion, with ROSA26-Panx1 under the control of an inducible SMC specific Cre (Myh11). This resulted in mice that could express only human Panx1, only in SMCs. After tamoxifen, these mice had increased blood pressure that was acutely decreased by the Panx1 inhibitor spironolactone. Control mice genetically devoid of Panx1 did not respond to spironolactone.

conclusionsThese data suggest Panx1 in SMCs could regulate the extent of sympathetic nerve constriction and blood pressure. The results also show the feasibility humanized Panx1-mouse models to test pharmacological candidates.

Indexed as

SpironolactoneVasoconstrictionAdenosine TriphosphateAnimalsBlood PressureConnexinsHumansMiceMyocytes, Smooth MuscleNerve Tissue ProteinsSympathetic Nervous SystemAdenosine TriphosphateConnexinsNerve Tissue ProteinsPANX1 protein, humanPanx1 protein, mouseSpironolactoneblood pressurepannexinsmooth musclespironolactonesympathetic nerve

Identifiers

PMID36448464
PMCPMC9851955
OpenAlexW4310376392

What Socratic 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 Socratic graph.