Evidence map›Paper›PMID 27199131›Full record

ArticleAmerican journal of physiology. Heart and circulatory physiology2016

Androgen-sensitive hypertension associated with soluble guanylate cyclase-α1 deficiency is mediated by 20-HETE.

Ana C Dordea, Sara Vandenwijngaert, Victor Garcia, Robert E T Tainsh, Daniel I Nathan, Kaitlin Allen, Michael J Raher, Laurel T Tainsh, Fan Zhang, Wolfgang S Lieb and 14 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
5.5field-weighted citation impact, top 5% 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

4 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Effect of Cytochrome P450 Metabolites of Arachidonic Acid in Nephrology.Journal of the American Society of Nephrology : JASN · 2017
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 7 institutions in 2 countries.

Ana C DordeaAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Sara VandenwijngaertAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Victor GarciaDepartment of Pharmacology, New York Medical College, Valhalla, New York;
Robert E T TainshAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Daniel I NathanAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Kaitlin AllenAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Michael J RaherAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Laurel T TainshAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Fan ZhangDepartment of Pharmacology, New York Medical College, Valhalla, New York;
Wolfgang S LiebAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Sarah MikelmanAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Andrew KirbyAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;
Christine StevensProgram in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Techonology, Cambridge, Massachusetts;
Robrecht ThoonenAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Allyson G HindleAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts;
Patrick Y SipsDivision of Cardiovascular Medicine, Department of Medicine Brigham and Women's Hospital, Boston, Massachusetts;
John R FalckDepartments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas;
Mark J DalyAnalytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Techonology, Cambridge, Massachusetts;
Peter BrouckaertDepartment for Biomedical Molecular Biology, Ghent University, Ghent, Belgium; and.
Kenneth D BlochAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts; Cardiology Division, Department of Medicine, Massachusetts General, Harvard Medical School, Boston, Massachusetts.
Donald B BlochAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts; Cardiology Division, Department of Medicine, Massachusetts General, Harvard Medical School, Boston, Massachusetts.
Rajeev MalhotraAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts; Cardiology Division, Department of Medicine, Massachusetts General, Harvard Medical School, Boston, Massachusetts.
Michal L SchwartzmanDepartment of Pharmacology, New York Medical College, Valhalla, New York;
Emmanuel S BuysAnesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital Research Institute, Harvard Medical School, Boston, Massachusetts; ebuys@mgh.harvard.edu.
Harvard University · USMassachusetts General Hospital · USNew York Medical College · USBrigham and Women's Hospital · USBroad Institute · USGhent University · BEThe University of Texas Southwestern Medical Center · US

Funding

Vasoregulatory Function of CYP2E1-Derived EicosanoidsP01HL034300 · NHLBI · NEW YORK MEDICAL COLLEGE · PI SCHWARTZMAN, MICHAL LANIADO · 1985 to 2015
$33.4M
MULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1M
BMPR2 and the Pathogenesis of Pulmonary HypertensionR01HL074352 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BLOCH, KENNETH D · 2003 to 2011
$3.7M
EET-Induced Cardioprotection: Role of Opioids and Nitric Oxide (NO)R01HL111392 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI AUCHAMPACH, JOHN A · 2012 to 2016
$2.2M
Role of Soluble Guanylate Cyclase Alpha 1 in Open Angle GlaucomaR01EY022746 · NEI · MASSACHUSETTS GENERAL HOSPITAL · PI BUYS, EMMANUEL S · 2012 to 2016
$2.0M
The Role of Bone Morphogenetic Proteins in Vascular CalcificationK08HL111210 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI MALHOTRA, RAJEEV · 2014 to 2018
$796k
NEI NIH HHS R01 EY022746NHLBI NIH HHS K08 HL111210NHLBI NIH HHS P01 HL034300NHLBI NIH HHS R01 HL074352NHLBI NIH HHS R01 HL111392NHLBI NIH HHS T32 HL007208
6 · The paper itself

Abstract

Dysregulated nitric oxide (NO) signaling contributes to the pathogenesis of hypertension, a prevalent and often sex-specific risk factor for cardiovascular disease. We previously reported that mice deficient in the α1-subunit of the NO receptor soluble guanylate cyclase (sGCα1 (-/-) mice) display sex- and strain-specific hypertension: male but not female sGCα1 (-/-) mice are hypertensive on an 129S6 (S6) but not a C57BL6/J (B6) background. We aimed to uncover the genetic and molecular basis of the observed sex- and strain-specific blood pressure phenotype. Via linkage analysis, we identified a suggestive quantitative trait locus associated with elevated blood pressure in male sGCα1 (-/-)S6 mice. This locus encompasses Cyp4a12a, encoding the predominant murine synthase of the vasoconstrictor 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE). Renal expression of Cyp4a12a in mice was associated with genetic background, sex, and testosterone levels. In addition, 20-HETE levels were higher in renal preglomerular microvessels of male sGCα1 (-/-)S6 than of male sGCα1 (-/-)B6 mice. Furthermore, treating male sGCα1 (-/-)S6 mice with the 20-HETE antagonist 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20-HEDE) lowered blood pressure. Finally, 20-HEDE rescued the genetic background- and testosterone-dependent impairment of acetylcholine-induced relaxation in renal interlobar arteries associated with sGCα1 deficiency. Elevated Cyp4a12a expression and 20-HETE levels render mice susceptible to hypertension and vascular dysfunction in a setting of sGCα1 deficiency. Our data identify Cyp4a12a as a candidate sex-specific blood pressure-modifying gene in the context of deficient NO-sGC signaling.

Indexed as

AndrogensAnimalsBlood PressureCytochrome P450 Family 4FemaleGenetic LinkageHydroxyeicosatetraenoic AcidsHypertensionKidneyMaleMiceMice, KnockoutQuantitative Trait LociSex FactorsSoluble Guanylyl CyclaseTestosterone20-hydroxy-5,8,11,14-eicosatetraenoic acidAndrogensCyp4a12a protein, mouseCytochrome P450 Family 4Hydroxyeicosatetraenoic AcidsSoluble Guanylyl CyclaseTestosterone20-HETEcytochrome P450hypertensionnitric oxidesoluble guanylate cyclasevascular function

Identifiers

PMID27199131
PMCPMC4935526
OpenAlexW2346214014

What OpenQuestion holds

Textmetadata
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Registered trials

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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.