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

The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.

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
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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.

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Crossref · 10.1161/hc0302.102597

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Research works printed but not linked: 9

  1. 10.1161/circ.96.2.575 · DOI
  2. 10.1161/circ.98.20.2154 · DOI
  3. 10.1161/circ.99.13.1706 · DOI
  4. 10.1161/str.28.8.1564 · DOI
  5. 10.1161/hyp.32.1.101 · DOI
  6. 10.1161/hyp.37.3.907 · DOI
  7. 10.1161/circ.101.8.886 · DOI
  8. 10.1161/str.29.9.1876 · DOI
  9. 10.1161/circ.100.17.1798 · DOI

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Metadata

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 › Cardiology and Cardiovascular Medicine › 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

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