Evidence map›Paper›PMID 25712724›Full record

ArticleHypertension (Dallas, Tex. : 1979)2015

Brainstem hypoxia contributes to the development of hypertension in the spontaneously hypertensive rat.

Nephtali Marina, Richard Ang, Asif Machhada, Vitaliy Kasymov, Anastassios Karagiannis, Patrick S Hosford, Valentina Mosienko, Anja G Teschemacher, Pirkko Vihko, Julian F R Paton and 2 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.

  1. Pooled it
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  3. Resting regional brain activity and connectivity vary with resting blood pressure but not muscle sympathetic nerve activity in normotensive humans: An exploratory study.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2019
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  20. Mechanosensory Signaling in Astrocytes.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
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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

12 authors at 1 institution in 1 country.

Nephtali MarinaFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.). n.marina@ucl.ac.uk a.gourine@ucl.ac.uk.
Richard AngFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Asif MachhadaFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Vitaliy KasymovFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Anastassios KaragiannisFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Patrick S HosfordFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Valentina MosienkoFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Anja G TeschemacherFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Pirkko VihkoFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Julian F R PatonFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Sergey KasparovFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.).
Alexander V GourineFrom the Centre for Cardiovascular and Metabolic Neuroscience (N.M., R.A., A.M., V.K., A.K., P.S.H., A.V.G.), Department of Clinical Pharmacology and Experimental Therapeutics (N.M., P.S.H.), and Neuroscience, Physiology and Pharmacology (R.A., A.M., V.K., A.K., A.V.G.), University College London, London, United Kingdom; School of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom (V.M., A.G.T., J.F.R.P., S.K.); and Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland (P.V.). n.marina@ucl.ac.uk a.gourine@ucl.ac.uk.
University of Bristol · GB

Funding

British Heart Foundation FS/13/5/29927British Heart Foundation PG/09/064/27886British Heart Foundation RG/12/6/29670British Heart Foundation RG/14/4/30736Medical Research Council G0901948Wellcome Trust 095064
6 · The paper itself

Abstract

Systemic arterial hypertension has been previously suggested to develop as a compensatory condition when central nervous perfusion/oxygenation is compromised. Principal sympathoexcitatory C1 neurons of the rostral ventrolateral medulla oblongata (whose activation increases sympathetic drive and the arterial blood pressure) are highly sensitive to hypoxia, but the mechanisms of this O2 sensitivity remain unknown. Here, we investigated potential mechanisms linking brainstem hypoxia and high systemic arterial blood pressure in the spontaneously hypertensive rat. Brainstem parenchymal PO2 in the spontaneously hypertensive rat was found to be ≈15 mm Hg lower than in the normotensive Wistar rat at the same level of arterial oxygenation and systemic arterial blood pressure. Hypoxia-induced activation of rostral ventrolateral medulla oblongata neurons was suppressed in the presence of either an ATP receptor antagonist MRS2179 or a glycogenolysis inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol, suggesting that sensitivity of these neurons to low PO2 is mediated by actions of extracellular ATP and lactate. Brainstem hypoxia triggers release of lactate and ATP which produce excitation of C1 neurons in vitro and increases sympathetic nerve activity and arterial blood pressure in vivo. Facilitated breakdown of extracellular ATP in the rostral ventrolateral medulla oblongata by virally-driven overexpression of a potent ectonucleotidase transmembrane prostatic acid phosphatase results in a significant reduction in the arterial blood pressure in the spontaneously hypertensive rats (but not in normotensive animals). These results suggest that in the spontaneously hypertensive rat, lower PO2 of brainstem parenchyma may be associated with higher levels of ambient ATP and l-lactate within the presympathetic circuits, leading to increased central sympathetic drive and concomitant sustained increases in systemic arterial blood pressure.

Indexed as

Adenosine TriphosphateAnimalsBlood PressureBrain StemDisease Models, AnimalDisease ProgressionFemaleHypertensionHypoxia-Ischemia, BrainLactic AcidMaleRatsRats, Inbred SHRRats, WistarSympathetic Nervous SystemAdenosine TriphosphateLactic Acidadenosine triphosphatehypertensionhypoxialactic acidsympathetic nervous system

Identifiers

PMID25712724
PMCPMC4354460
OpenAlexW2136720542

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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.