| Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans. | |
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MedLine Citation:
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PMID: 16717144 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Previous studies suggest that neuronal norepinephrine transporter function may regulate the distribution of sympathetic activity among blood vessels, heart, and kidney; we tested the functional relevance in humans. Sixteen healthy men (26+/-1 years) ingested 8 mg of the selective norepinephrine reuptake transporter inhibitor reboxetine or a matching placebo on 2 separate days in a double-blind, randomized, crossover fashion. We monitored heart rate, thoracic bioimpedance, blood pressure, glomerular filtration rate, and renal blood flow. Ninety minutes after ingestion of the test medication, subjects were tilted to a 45 degrees head-up position, where they remained for an additional 30 minutes. Reboxetine increased supine systolic blood pressure through an increase in cardiac output whereas systemic vascular resistance decreased. Furthermore, reboxetine increased heart rate, particularly with a head-up tilt. Supine plasma renin activity was 0.71+/-0.15 ng angiotensin (Ang)/L per mL/h with placebo and 0.36+/-0.07 ngAng/L per mL/h with reboxetine (P<0.01). Supine plasma Ang II concentrations were also decreased with reboxetine. Both plasma renin activity and Ang II concentrations remained suppressed during head-up tilt. On placebo, renal vascular resistance increased with head-up tilt. The response was abolished with norepinephrine reuptake inhibition. We conclude that norepinephrine reuptake function profoundly influences the distribution of sympathetic activity between the heart, vasculature, and kidney in humans. All of these changes are physiologically relevant because they lead to corresponding changes in organ function. |
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Authors:
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Antje F Mayer; Christoph Schroeder; Karsten Heusser; Jens Tank; André Diedrich; Roland E Schmieder; Friedrich C Luft; Jens Jordan |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2006-05-22 |
Journal Detail:
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Title: Hypertension Volume: 48 ISSN: 1524-4563 ISO Abbreviation: Hypertension Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-06-23 Completed Date: 2006-07-19 Revised Date: 2007-11-15 |
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: 120-6 Citation Subset: IM |
Affiliation:
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Franz-Volhard-Clinical Research Center, Medical Faculty of the Charité, Max-Delbrueck Centrum, and HELIOS Klinikum, Berlin, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic Uptake Inhibitors
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pharmacology* Adult Angiotensin II / blood Blood Pressure / drug effects Cross-Over Studies Double-Blind Method Glomerular Filtration Rate / drug effects Heart Rate / drug effects Hemodynamics / drug effects Humans Male Morpholines / pharmacology* Norepinephrine / metabolism Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*, metabolism Posture Renal Circulation / drug effects Renin / blood Sympathetic Nervous System / drug effects* |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic Uptake Inhibitors; 0/Morpholines; 0/Norepinephrine Plasma Membrane Transport Proteins; 11128-99-7/Angiotensin II; 51-41-2/Norepinephrine; 98769-81-4/reboxetine; EC 3.4.23.15/Renin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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