Evidence map›Paper›PMID 23702660›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2013

Circulating blood endothelial nitric oxide synthase contributes to the regulation of systemic blood pressure and nitrite homeostasis.

Katherine C Wood, Miriam M Cortese-Krott, Jason C Kovacic, Audrey Noguchi, Virginia B Liu, Xunde Wang, Nalini Raghavachari, Manfred Boehm, Gregory J Kato, Malte Kelm and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed
7.0field-weighted citation impact, top 2% 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

64 citing papers in PubMed, 119 citations in OpenAlex.

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  13. Photobiomodulation and nitric oxide signaling.Nitric oxide : biology and chemistry · 2023
    Review
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4 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

11 authors at 1 institution in 1 country.

Katherine C WoodHematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Miriam M Cortese-Krott
Jason C Kovacic
Audrey Noguchi
Virginia B Liu
Xunde Wang
Nalini Raghavachari
Manfred Boehm
Gregory J Kato
Malte Kelm
Mark T Gladwin
Mount Sinai Hospital · US

Funding

NHLBI Animal Program DivisionZIGHL006020 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI CLARK, TANNIA · 2009 to 2025
$47.3M
Vascular remodeling in patients with rare genetic disordersZIAHL006077 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BOEHM, MANFRED · 2010 to 2025
$22.9M
Storage Lesion in Banked Blood Due to Disruption of Nitric Oxide HomeostasisR01HL098032 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Mark T Gladwin · 2009 to 2026
$12.5M
Murine models of vascular remodelingZIAHL006078 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BOEHM, MANFRED · 2010 to 2025
$11.4M
Myoglobin as a Nitrite Reductase that Regulates Hypoxic Cardiac NO SignalingR01HL096973 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GLADWIN, MARK T, SHIVA, SRUTI · 2010 to 2013
$1.5M
Dietary nitrate activation of PPARgamma improves insulin sensitivityRC1DK085852 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN, GLADWIN, MARK T · 2009 to 2010
$999k
Blood Studies of Endothelial Function and Systemic InflammationZIAHL006013 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI KATO, GREGORY · 2009 to 2013
$680k
Intramural NIH HHS ZIA HL006013NHLBI NIH HHS R01 HL096973NHLBI NIH HHS R01HL096973NHLBI NIH HHS R01 HL098032NHLBI NIH HHS R01HL098032NIDDK NIH HHS RC1 DK085852NIDDK NIH HHS RC1DK085852
6 · The paper itself

Abstract

objectiveMice genetically deficient in endothelial nitric oxide synthase (eNOS(-/-)) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. Although the current paradigm holds that this bioactivity derives specifically from the expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. APPROACH AND

resultsTo test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted wild-type and eNOS(-/-) mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NG-nitroarginine methyl ester and repristinated by the NOS substrate L-arginine and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert (14)C-arginine into (14)C-citrulline in NOS-dependent fashion.

conclusionsThese are the first studies to definitively establish a role for a blood-borne eNOS, using cross-transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect.

Indexed as

AnimalsArginineBlood PressureCarbon RadioisotopesCitrullineEndothelium, VascularEnzyme InhibitorsErythrocytesHomeostasisHypertensionMiceMice, KnockoutNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide Synthase Type IIINitritesArginineCarbon RadioisotopesCitrullineEnzyme InhibitorsNG-Nitroarginine Methyl EsterNitric OxideNitric Oxide Synthase Type IIINitritesNos3 protein, mousebloodblood pressurebone marrow transplantnitric oxide synthase

Identifiers

PMID23702660
PMCPMC3864011
OpenAlexW2145507715

What OpenQuestion holds

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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.