This Article 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 Esler, M. Articles by Korner, P. Search for Related Content PubMed PubMed Citation Articles by Esler, M. Articles by Korner, P. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure

Hypertension, Vol 3, 149-156, Copyright © 1981 by American Heart Association

ARTICLES

Norepinephrine kinetics in essential hypertension. Defective neuronal uptake of norepinephrine in some patients

M Esler, G Jackman, A Bobik, P Leonard, D Kelleher, H Skews, G Jennings and P Korner

To assess sympathetic nervous system function in essential hypertension, we measured the rates of release to and removal from plasma of the sympathetic neurotransmitter, norepinephrine. In normal subjects, disappearance of tritiated l-norepinephrine from plasma, after infusion to steady state, was biexponential, with t1 1/2 = 2.0 +/- 0.4 minutes (mean +/- standard deviation) and t2 1/2 = 33 +/- 15 minutes. The rapid component of removal seemed to represent neuronal uptake of norepinephrine: the t1 1/2 was lengthened by the selective inhibitor of neuronal norepinephrine uptake, desipramine; it was not changed by the extraneuronal uptake blocker, cortisol; and it was prolonged in patients with peripheral sympathetic nerve dysfunction (idiopathic autonomic insufficiency). In eight of 37 hypertensive patients, the t1 1/2 was greater than 2.8 minutes (range, 3.3-6.0 min), longer than in any normal subject; this appears to be presumptive evidence of the existence of defective neuronal norepinephrine uptake. In these patients the rate of spillover of norepinephrine to plasma, of transmitter escaping uptake after release, was 0.73 +/- 0.39 micrograms/m2/min (4.3 +/- 2.3 nmoles/m2/min), higher than in normal subjects, 0.36 +/- 0.14 micrograms/m2/min (2.1 +/- 0.8 nmoles/m2/min) (p less than 0.01). A defect in neuronal uptake of norepinephrine, by exposing adrenergic receptors to high local norepinephrine concentration, may be important in the pathogenesis of blood pressure elevation in some patients with essential hypertension.

This article has been cited by other articles:

				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]

				P. M. Grossman, O. A. Linares, M. A. Supiano, H. Oral, R. H. Mehta, and M. R. Starling Cardiac-specific norepinephrine mass transport and its relationship to left ventricular size and systolic performance Am J Physiol Heart Circ Physiol, August 1, 2004; 287(2): H878 - H888. [Abstract] [Full Text] [PDF]

				L. D. Jayanthi, D. J. Samuvel, and S. Ramamoorthy Regulated Internalization and Phosphorylation of the Native Norepinephrine Transporter in Response to Phorbol Esters: EVIDENCE FOR LOCALIZATION IN LIPID RAFTS AND LIPID RAFT-MEDIATED INTERNALIZATION J. Biol. Chem., April 30, 2004; 279(18): 19315 - 19326. [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. K. Hahn, D. Robertson, and R. D. Blakely A Mutation in the Human Norepinephrine Transporter Gene (SLC6A2) Associated with Orthostatic Intolerance Disrupts Surface Expression of Mutant and Wild-Type Transporters J. Neurosci., June 1, 2003; 23(11): 4470 - 4478. [Abstract] [Full Text] [PDF]

				U. Sung, S. Apparsundaram, A. Galli, K. M. Kahlig, V. Savchenko, S. Schroeter, M. W. Quick, and R. D. Blakely A Regulated Interaction of Syntaxin 1A with the Antidepressant-Sensitive Norepinephrine Transporter Establishes Catecholamine Clearance Capacity J. Neurosci., March 1, 2003; 23(5): 1697 - 1709. [Abstract] [Full Text] [PDF]

				M. van Onna, A. J.H.M. Houben, A. A. Kroon, T. K.A. Wierema, D. Koster, J. M.A. van Engelshoven, and P. W. de Leeuw Asymmetry of Renal Blood Flow in Patients With Moderate to Severe Hypertension Hypertension, January 1, 2003; 41(1): 108 - 113. [Abstract] [Full Text] [PDF]

				M. S. Rumantir, D. M. Kaye, G. L. Jennings, M. Vaz, J. A. Hastings, and M. D. Esler Phenotypic Evidence of Faulty Neuronal Norepinephrine Reuptake in Essential Hypertension Hypertension, November 1, 2000; 36(5): 824 - 829. [Abstract] [Full Text] [PDF]

				M. A. Supiano, R. V. Hogikyan, M. A. Sidani, A. T. Galecki, and J. L. Krueger Sympathetic nervous system activity and alpha -adrenergic responsiveness in older hypertensive humans Am J Physiol Endocrinol Metab, March 1, 1999; 276(3): E519 - E528. [Abstract] [Full Text] [PDF]

				C. M. Stein, R. Nelson, H. B. He, M. Wood, and A. J. J. Wood Norepinephrine Release in the Human Forearm : Effects of Epinephrine Hypertension, November 1, 1997; 30(5): 1078 - 1084. [Abstract] [Full Text]

				M.-C. Jacobs, J. W. M. Lenders, J. J. Willemsen, and T. Thien Adrenomedullary Secretion of Epinephrine Is Increased in Mild Essential Hypertension Hypertension, June 1, 1997; 29(6): 1303 - 1308. [Abstract] [Full Text]

				D. S. GOLDSTEIN, P. D. LEVINSON, R. ZIMLICHMAN, A. PITTERMAN, R. STULL, and H. R. KEISER Clonidine Suppression Testing in Essential Hypertension Ann Intern Med, January 1, 1985; 102(1): 42 - 48. [Abstract] [PDF]