This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Rumantir, M. S. Articles by Esler, M. D. Search for Related Content PubMed PubMed Citation Articles by Rumantir, M. S. Articles by Esler, M. D. Related Collections Other hypertension Autonomic, reflex, and neurohumoral control of circulation Genetics of cardiovascular disease

(Hypertension. 2000;36:824.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension

Magdalena S. Rumantir; David M. Kaye; Garry L. Jennings; Mario Vaz; Jacqueline A. Hastings; Murray D. Esler

From the Baker Medical Research Institute and Alfred Baker Medical Unit of the Alfred Hospital, Melbourne, Australia. Dr Vaz’s present address is Department of Physiology, St John’s Medical College, Bangalore, India.

Correspondence to Dr Magdalena S. Rumantir, Baker Medical Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia. E-mail magdalena.rumantir{at}baker.edu.au

Abstract—Previous reports suggest that neuronal norepinephrine (NE) reuptake may be impaired in essential hypertension, perhaps because of dysfunction of the NE transporter, although the evidence is inconclusive. To further test this proposition, we applied phenotypically relevant radiotracer methodology, infusion of tritiated NE and quantification of NE metabolites, to 34 healthy lean subjects (body mass index <27.0 kg/m²), 19 overweight (body mass index >28.0 kg/m²) but otherwise healthy normotensive subjects, 13 untreated lean patients with essential hypertension, and 14 obesity-related hypertensives. Spillover of NE from the heart was increased in lean hypertensives only (mean±SD 33.4±20.6 versus 16.1±11.7 ng/min in lean normotensives, P<0.05), but this could have resulted from high cardiac sympathetic nerve firing rates, faulty NE reuptake, or both. The arterial plasma concentration of 3-methoxy-4-hydroxylphenylglycol, an extraneuronal metabolite of NE, was elevated in lean hypertensives only (3942±1068 versus 3055±888 pg/mL in healthy subjects, P<0.05). The fractional extraction of plasma tritiated NE in passage through the heart, determined on the basis of neuronal NE uptake, was reduced in lean essential hypertensives (0.65±0.19 versus 0.81±0.11 in healthy subjects, P<0.05). Cardiac release of the tritiated NE metabolite [³H]dihydroxylphenylglycol, produced intraneuronally by monoamine oxidase after uptake of [³H]NE by the transporter, was reduced in lean hypertensives only (992±1435 versus 4588±3189 dpm/min in healthy subjects, P<0.01) These findings suggest that neuronal reuptake of NE is impaired in essential hypertension. Through amplification of the neural signal, such a defect could constitute a neurogenic variant of essential hypertension. In obesity-related hypertension, there was no phenotypic evidence of NE transporter dysfunction.

Key Words: nervous system, sympathetic • norepinephrine • obesity • heart • hypertension, obesity

This article has been cited by other articles:

				M. M. Fung, C. Nguyen, P. Mehtani, R. M. Salem, B. Perez, B. Thomas, M. Das, N. J. Schork, S. K. Mahata, M. G. Ziegler, et al. Genetic Variation Within Adrenergic Pathways Determines In Vivo Effects of Presynaptic Stimulation in Humans Circulation, January 29, 2008; 117(4): 517 - 525. [Abstract] [Full Text] [PDF]

				M. Esler, M. Alvarenga, C. Pier, J. Richards, A. El-Osta, D. Barton, D. Haikerwal, D. Kaye, M. Schlaich, L. Guo, et al. The neuronal noradrenaline transporter, anxiety and cardiovascular disease J Psychopharmacol, July 1, 2006; 20(4_suppl): 60 - 66. [Abstract] [PDF]

				A. F. Mayer, C. Schroeder, K. Heusser, J. Tank, A. Diedrich, R. E. Schmieder, F. C. Luft, and J. Jordan Influences of Norepinephrine Transporter Function on the Distribution of Sympathetic Activity in Humans Hypertension, July 1, 2006; 48(1): 120 - 126. [Abstract] [Full Text] [PDF]

				M. K. Ikram, J. C.M. Witteman, J. R. Vingerling, M. M.B. Breteler, A. Hofman, and P. T.V.M. de Jong Retinal Vessel Diameters and Risk of Hypertension: The Rotterdam Study Hypertension, February 1, 2006; 47(2): 189 - 194. [Abstract] [Full Text] [PDF]

				M. E. Alvarenga, J. C. Richards, G. Lambert, and M. D. Esler Psychophysiological Mechanisms in Panic Disorder: A Correlative Analysis of Noradrenaline Spillover, Neuronal Noradrenaline Reuptake, Power Spectral Analysis of Heart Rate Variability, and Psychological Variables Psychosom Med, January 1, 2006; 68(1): 8 - 16. [Abstract] [Full Text] [PDF]

				G. Eisenhofer, I. J. Kopin, and D. S. Goldstein Catecholamine Metabolism: A Contemporary View with Implications for Physiology and Medicine Pharmacol. Rev., September 1, 2004; 56(3): 331 - 349. [Abstract] [Full Text] [PDF]

				T. Kawada, T. Miyamoto, K. Uemura, K. Kashihara, A. Kamiya, M. Sugimachi, and K. Sunagawa Effects of neuronal norepinephrine uptake blockade on baroreflex neural and peripheral arc transfer characteristics Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2004; 286(6): R1110 - R1120. [Abstract] [Full Text] [PDF]

				O. Grisk and R. Rettig Interactions between the sympathetic nervous system and the kidneys in arterial hypertension Cardiovasc Res, February 1, 2004; 61(2): 238 - 246. [Abstract] [Full Text] [PDF]

				M. P. Schlaich, E. Lambert, D. M. Kaye, Z. Krozowski, D. J. Campbell, G. Lambert, J. Hastings, A. Aggarwal, and M. D. Esler Sympathetic Augmentation in Hypertension: Role of Nerve Firing, Norepinephrine Reuptake, and Angiotensin Neuromodulation Hypertension, February 1, 2004; 43(2): 169 - 175. [Abstract] [Full Text] [PDF]

				M. P. Schlaich, D. M. Kaye, E. Lambert, M. Sommerville, F. Socratous, and M. D. Esler Relation Between Cardiac Sympathetic Activity and Hypertensive Left Ventricular Hypertrophy Circulation, August 5, 2003; 108(5): 560 - 565. [Abstract] [Full Text] [PDF]

				J. Tank, C. Schroeder, A. Diedrich, E. Szczech, S. Haertter, A. M. Sharma, F. C. Luft, and J. Jordan Selective Impairment in Sympathetic Vasomotor Control With Norepinephrine Transporter Inhibition Circulation, June 17, 2003; 107(23): 2949 - 2954. [Abstract] [Full Text] [PDF]

				G. Horvath, A. Torbati, G. E. Conner, M. Salathe, and A. Wanner Systemic Ovalbumin Sensitization Downregulates Norepinephrine Uptake by Rabbit Aortic Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 746 - 751. [Abstract] [Full Text] [PDF]

				M. Esler, J. Hastings, G. Lambert, D. Kaye, G. Jennings, and D. R. Seals The influence of aging on the human sympathetic nervous system and brain norepinephrine turnover Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R909 - R916. [Abstract] [Full Text] [PDF]

				A. Cabassi, S. Vinci, A. M. Cantoni, F. Quartieri, L. Moschini, S. Cavazzini, A. Cavatorta, and A. Borghetti Sympathetic Activation in Adipose Tissue and Skeletal Muscle of Hypertensive Rats Hypertension, February 1, 2002; 39(2): 656 - 661. [Abstract] [Full Text] [PDF]

				A. Cabassi, S. Vinci, F. Quartieri, L. Moschini, and A. Borghetti Norepinephrine Reuptake Is Impaired in Skeletal Muscle of Hypertensive Rats In Vivo Hypertension, February 1, 2001; 37(2): 698 - 702. [Abstract] [Full Text] [PDF]