Published Online
on April 12, 2004

A more recent version of this article appeared on June 1, 2004

This Article Full Text (PDF) All Versions of this Article: 43/6/1227    most recent 01.HYP.0000127305.87552.d6v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eldadah, B. A. Articles by Goldstein, D. S. Search for Related Content PubMed PubMed Citation Articles by Eldadah, B. A. Articles by Goldstein, D. S. Related Collections Other etiology Receptor pharmacology Nuclear cardiology and PET

Submitted on September 30, 2003
Revised on November 19, 2003

Cardiac Uptake-1 Inhibition by High Circulating Norepinephrine Levels in Patients with Pheochromocytoma

Basil A. Eldadah^*; Karel Pacak; Graeme Eisenhofer; Courtney Holmes; Irwin J. Kopin; and David S. Goldstein

From the Clinical Neurocardiology Section (B.A.E., G.E., C.H., I.J.K., D.S.G.), National Institute of Neurological Disorders and Stroke, and the Pediatric and Reproductive Endocrinology Branch (K.P.), National Institute of Child Health and Development, National Institutes of Health.

^* To whom correspondence should be addressed. E-mail: eldadahb{at}ninds.nih.gov.

Abstract--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 µmol/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 (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.

Key words: heart • norepinephrine • pheochromocytoma • radiography

This article has been cited by other articles:

				D. S. Goldstein Genotype and Vascular Phenotype Linked by Catecholamine Systems Circulation, January 29, 2008; 117(4): 458 - 461. [Full Text] [PDF]

				M. Sesay, P. Tauzin-Fin, P. Gosse, P. Ballanger, and P. Maurette Real-Time Heart Rate Variability and Its Correlation with Plasma Catecholamines During Laparoscopic Adrenal Pheochromocytoma Surgery Anesth. Analg., January 1, 2008; 106(1): 164 - 170. [Abstract] [Full Text] [PDF]

				M. Hadi, C. C. Chen, M. Whatley, K. Pacak, and J. A. Carrasquillo Brown Fat Imaging with 18F-6-Fluorodopamine PET/CT, 18F-FDG PET/CT, and 123I-MIBG SPECT: A Study of Patients Being Evaluated for Pheochromocytoma J. Nucl. Med., July 1, 2007; 48(7): 1077 - 1083. [Abstract] [Full Text] [PDF]

				P. A FITZGERALD, R. E GOLDSBY, J. P HUBERTY, D. C PRICE, R. A HAWKINS, J. J VEATCH, F. D. CRUZ, T. M JAHAN, C. A LINKER, L. DAMON, et al. Malignant Pheochromocytomas and Paragangliomas: A Phase II Study of Therapy with High-Dose 131I-Metaiodobenzylguanidine (131I-MIBG). Ann. N.Y. Acad. Sci., August 1, 2006; 1073: 465 - 490. [Abstract] [Full Text] [PDF]