Evidence map›Paper›PMID 25350545›Full record

ArticlePloS one2014

β2-Adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats.

Hisashi Nagai, Ichiro Kuwahira, Daryl O Schwenke, Hirotsugu Tsuchimochi, Akina Nara, Tadakatsu Inagaki, Sayoko Ogura, Yutaka Fujii, Keiji Umetani, Tatsuo Shimosawa and 4 more

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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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

14 authors at 9 institutions in 3 countries.

Hisashi NagaiDepartment of Forensic Medicine, Tokyo Medical and Dental University, Tokyo, Japan; Department of Forensic Medicine, The University of Tokyo, Tokyo, Japan; Department of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
Ichiro KuwahiraDepartment of Pulmonary Medicine, Tokai University Tokyo Hospital, Tokyo, Japan.
Daryl O SchwenkeDepartment of Physiology-Heart Otago, University of Otago, Dunedin, New Zealand.
Hirotsugu TsuchimochiDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Akina NaraDepartment of Forensic Medicine, The University of Tokyo, Tokyo, Japan.
Tadakatsu InagakiDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Sayoko OguraDepartment of Forensic Medicine, The University of Tokyo, Tokyo, Japan; Division of Laboratory Medicine, Department of Pathology and Microbiology, Faculty of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Yutaka FujiiDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
Keiji UmetaniJapan Synchrotron Radiation Research Institute, Hyogo, Japan.
Tatsuo ShimosawaDepartment of Clinical Laboratory Medicine, The University of Tokyo, Tokyo, Japan.
Ken-ichi YoshidaDepartment of Forensic Medicine, The University of Tokyo, Tokyo, Japan; Department of Forensic Medicine, Tokyo Medical University, Tokyo, Japan.
James T PearsonMonash Biomedical Imaging Facility and Department of Physiology, Monash University, Melbourne, Clayton, Victoria, Australia; Australian Synchrotron, Clayton, Victoria, Australia.
Koichi UemuraDepartment of Forensic Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Mikiyasu ShiraiDepartment of Cardiac Physiology, National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan.
National Cerebral and Cardiovascular Center · JPThe University of Tokyo · JPJapan Synchrotron Radiation Research Institute · JPMonash University · AUNihon University · JPTokai University Hospital · JPTokyo Medical and Dental University · JPTokyo Medical University · JPUniversity of Otago · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In sleep apnea syndrome (SAS), intermittent hypoxia (IH) induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV) during sleep, which presumably contribute to pulmonary arterial hypertension (PAH). However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH) was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4-21% O2 for 8 h/d for 6 w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β(1, 2)-blocker) augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker) had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR) was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K)), protein kinase B (Akt), and endothelial nitric oxide synthase (eNOS) were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway.

Indexed as

VasoconstrictionAdrenergic beta-2 Receptor AntagonistsAnimalsBlood PressureClass Ia Phosphatidylinositol 3-KinaseDisease Models, AnimalDisease ProgressionHypertension, PulmonaryHypertrophy, Right VentricularHypoxiaMaleNadololNitric Oxide Synthase Type IIIPhosphorylationProto-Oncogene Proteins c-aktPulmonary ArteryAdrenergic beta-2 Receptor AntagonistsClass Ia Phosphatidylinositol 3-KinaseNadololNitric Oxide Synthase Type IIIProto-Oncogene Proteins c-aktReceptors, Adrenergic, beta-1Receptors, Adrenergic, beta-2

Identifiers

PMID25350545
PMCPMC4211686
OpenAlexW2089414614

What OpenQuestion holds

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LicenceCC BY
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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.