CoChat
Sign Up
Cited by 127Cardiovascular Syncope and Autonomic DisordersHeart Rate Variability and Autonomic ControlCardiac electrophysiology and arrhythmias

Selective Norepinephrine Reuptake Inhibition as a Human Model of Orthostatic Intolerance

Schroeder, Christoph, Tank, Jens, Boschmann, Michael, Diedrich, Andre, Sharma, Arya M., Biaggioni, Italo, Luft, Friedrich C., Jordan, Jens·2002·Circulation
DOI 10.1161/hc0302.102597
Open this paper in CoChat — free account

Abstract

Background — Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance. Methods and Results — We studied the effect of the selective NET blocker reboxetine and placebo in a randomized, double-blind, crossover fashion on cardiovascular responses to cold pressor testing, handgrip testing, and a graded head-up tilt test (HUT) in 18 healthy subjects. In a subset, we determined isoproterenol and phenylephrine sensitivities. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. In the supine position, heart rate was 65±2 bpm with placebo and 71±3 bpm with reboxetine. At 75° HUT, heart rate was 84±3 and 119±4 bpm with placebo and with reboxetine ( P <0.0001). Mean arterial pressure was 85±2 with placebo and 91±2 mm Hg with reboxetine while supine ( P <0.01) and 88±2 mm Hg and 90±3 mm Hg at 75° HUT. Blood pressure responses to cold pressor and handgrip testing were attenuated with reboxetine. Reboxetine increased the sensitivity to the chronotropic effect of isoproterenol and the pressor effect of phenylephrine. Vasovagal reactions occurred in 9 subjects on placebo and in 1 subject on reboxetine. Conclusions — Selective NET blockade creates a phenotype that resembles idiopathic orthostatic intolerance. This observation supports the hypothesis that disordered norepinephrine uptake mechanisms can contribute to human cardiovascular disease. Our study also suggests that NET inhibition might be useful in preventing vasovagal reactions.

Integrity signals

Registry

Crossref · 10.1161/hc0302.102597

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Iatrogenic inhibition of the norepinephrine transporter has been shown to engender a POTS-like state, increase upright heart rate, and exacerbate symptoms in POTS patients.

    “Iatrogenic inhibition of the norepinephrine transporter has also been shown to engender a POTS-like state, increase upright heart rate, and exacerbate symptoms in POTS patients (46-49).”

    From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [48]

  • Administration of reboxetine, a norepinephrine transporter inhibitor, to healthy controls provoked hemodynamic changes consistent with POTS.

    “Administration of reboxetine, a norepinephrine transporter inhibitor, to healthy controls provoked hemodynamic changes consistent with POTS (48).”

    From Postural orthostatic tachycardia syndrome: mechanisms and new therapies (2020) · cites this paper as [48]

Cites

Flagged first, then by citations

1 of the 32 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Schroeder, C., Tank, J., Boschmann, M., Diedrich, A., Sharma, A. M., Biaggioni, I., Luft, F. C., & Jordan, J.
Affiliations
  • Vanderbilt University (US)
  • From the Clinical Research Center (C.S., J.T., A.M.S., F.C.L., J.J.), HELIOS Klinkum-Berlin, Franz Volhard Clinic, Medical Faculty of the Charité, Humboldt-University, Berlin, Germany; German Institute of Human Nutrition (M.B.), Potsdam, Germany; and Autonomic Dysfunction Service (A.D., I.B.), Vanderbilt University, Nashville, Tenn.
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2002-01-22
Volume
105
Issue
3
Pages
347-353
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/hc0302.102597
OpenAlex
W2053706211
Cited by
127
References
32
Citations by year
2025: 2 · 2024: 7 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 2 · 2014: 5 · 2013: 8 · 2012: 6
FWCI
10.16
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders
Deutsche Forschungsgemeinschaft
Topics
  • Health Sciences › Medicine › Surgery › Cardiovascular Syncope and Autonomic Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
Keywords
norepinephrine transporter, norepinephrine reuptake inhibition, reboxetine, orthostatic intolerance, vasovagal reaction, heart rate, blood pressure, phenylephrine sensitivity, cold pressor test, head-up tilt, handgrip test
MeSH terms
Reboxetine, Adrenergic Agonists, Adult, Autonomic Nervous System, Biological Transport, Blood Pressure, Double-Blind Method, Female, Heart Rate, Humans, Isoproterenol, Male, Morpholines, Norepinephrine, Phenylephrine, Posture, Reflex, Syndrome, Tachycardia, Baroreflex, Cross-Over Studies, Tilt-Table Test, Adrenergic Uptake Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review