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(Hypertension. 2004;43:1227.)
© 2004 American Heart Association, Inc.

Scientific Contributions

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; 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.

Correspondence to Dr Basil A. Eldadah, Building 10, Room 6N252, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620. E-mail eldadahb{at}ninds.nih.gov

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

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