| Cardiac uptake-1 inhibition by high circulating norepinephrine levels in patients with pheochromocytoma. | |
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MedLine Citation:
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PMID: 15078865 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neuronal reuptake (uptake-1) constitutes the main route of inactivation of the sympathetic neurotransmitter norepinephrine in the heart and therefore contributes importantly to cardiac sympathetic neuroeffector function. In laboratory animals and in vitro preparations, half saturation of the transporter occurs at norepinephrine concentrations of 0.1 to 1 micromol/L. This study addressed whether endogenous norepinephrine can attain high enough plasma concentrations in humans to inhibit cardiac uptake-1. Patients with increased plasma norepinephrine levels due to pheochromocytoma were assessed by 6-[18F]fluorodopamine positron emission tomography. Above an antecubital venous plasma concentration of 3 nmol/L (approximately 500 pg/mL), left ventricular myocardial 6-[18F]fluorodopamine-derived radioactivity varied inversely with the logarithm of the plasma norepinephrine concentration (r=-0.77, P<0.0001). Reduction of plasma norepinephrine levels by treatment of the pheochromocytoma increased myocardial 6-[18F]fluorodopamine-derived radioactivity. At sufficiently high plasma concentrations, endogenous norepinephrine can compete with sympathetic imaging agents for uptake-1. The results call for caution in drawing quantitative conclusions about uptake-1 in the setting of high circulating concentrations of endogenous norepinephrine. |
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Authors:
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Basil A Eldadah; Karel Pacak; Graeme Eisenhofer; Courtney Holmes; Irwin J Kopin; David S Goldstein |
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Publication Detail:
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Type: Journal Article Date: 2004-04-12 |
Journal Detail:
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Title: Hypertension Volume: 43 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2004 Jun |
Date Detail:
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Created Date: 2004-05-28 Completed Date: 2004-10-28 Revised Date: 2005-11-17 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: United States |
Other Details:
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Languages: eng Pagination: 1227-32 Citation Subset: IM |
Affiliation:
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Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620, USA. eldadahb@ninds.nih.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenal Gland Neoplasms
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metabolism*,
radionuclide imaging Adult Aged Aged, 80 and over Binding, Competitive Dihydroxyphenylalanine / analogs & derivatives*, diagnostic use, pharmacokinetics False Negative Reactions Female Heart / innervation, radionuclide imaging* Humans Imaging, Three-Dimensional Liver / metabolism Male Middle Aged Myocardium / metabolism* Norepinephrine / blood* Norepinephrine Plasma Membrane Transport Proteins Pheochromocytoma / metabolism*, radionuclide imaging Radiopharmaceuticals / diagnostic use, pharmacokinetics Symporters / antagonists & inhibitors*, metabolism Tomography, Emission-Computed* |
| Chemical | |
Reg. No./Substance:
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0/Norepinephrine Plasma Membrane Transport Proteins; 0/Radiopharmaceuticals; 0/SLC6A2 protein, human; 0/Symporters; 51-41-2/Norepinephrine; 63-84-3/Dihydroxyphenylalanine; 75290-51-6/fluorodopa F 18 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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