Skip to main content
SpringerLink
Log in

Sympathetic nerve function

Assessment by radioisotope dilution analysis

  • REVIEW ARTICLE
  • Published:
Clinical Autonomic Research Aims and scope Submit manuscript

Abstract

Radioisotope dilution measurements of norepinephrine spillover (rate of entry of the transmitter into plasma) provide more accurate assessments of sympathoneural transmitter release than allowed by measurements of plasma catecholamine concentrations alone. Measurements of total body norepinephrine spillover, as an index of global sympathetic outflow, allow effects on plasma clearance to be distinguished from effects on release of catecholamines into plasma,while spillovers from specific tissues enable examination of regionalized sympathetic responses. However, spillovers of norepinephrine represent only a fraction of the transmitter that escapes neuronal and extraneuronal uptake after release by nerves. Numerous factors may influence this fraction and measures spillovers independently of transmitter release by nerves. Modified radioisotope dilution methods for assessment of rate processes operating within and between intracellular and extracellular compartments have further improved our understanding of the relationships of norepinephrine release, uptake, spillover, turnover, and metabolism. This article reviews the breadth of information about sympathetic nerve function attainable using catecholamine radioisotope dilution analyses against a backdrop of the relative advantages and methodological limitations associated with the methodology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Altszuler N, De Bodo RC, Steele R, Wall JS (1956) Measurement of size and turnover rate of body glucose pool by the isotope dilution method. Am J Physiol 187:15–24

    PubMed  Google Scholar 

  2. Åneman A, Eisenhofer G, Fandriks L, Friberg P (1995) Hepatomesenteric release and removal of norepinephrine in swine. Am J Physiol 268:R924–R930

    PubMed  Google Scholar 

  3. Åneman A, Eisenhofer G, Olbe L, Dalenback J, Nitescu P, Fandriks L, Friberg P (1996) Sympathetic discharge to mesenteric organs and the liver. Evidence for substantial mesenteric organ norepinephrine spillover. J Clin Invest 97:1640–1646

    PubMed  Google Scholar 

  4. Baily RG, Leuenberger U, Leaman G, Silber D, Sinoway LI (1991) Norepinephrine kinetics and cardiac output during nonhypotensive lower body negative pressure. Am J Physiol 260:H1708–H1712

    PubMed  Google Scholar 

  5. Beau SL, Saffitz JE (1994) Transmural heterogeneity of norepinephrine uptake in failing human hearts. J Am Coll Cardiol 23:579–585

    PubMed  Google Scholar 

  6. Best JD, Halter JB (1982) Release and clearance rates of epinephrine in man: importance of arterial measurements. J Clin Endocrinol Metab 55:263–268

    PubMed  Google Scholar 

  7. Bohm M, La Rosee K, Schwinger RH, Erdmann E (1995) Evidence for reduction of norepinephrine uptake sites in the failing human heart. J Am Coll Cardiol 25:146–153

    Article  PubMed  Google Scholar 

  8. Brick I, Hutchison KJ, Roddie IC (1967) Inactivation of circulating catecholamines in the human forearm. J Physiol 190:25P–26P

    PubMed  Google Scholar 

  9. Bristow MR, Ginsburg R, Umans V, Fowler M, Minobe W, Rasmussen R, Zera P, Menlove R, Shah P, Jamieson S, et al. (1986) Beta 1-and beta 2-adrenergic-receptor subpopulations in non-failing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective beta 1-receptor down-regulation in heart failure. Circ Res 59:297–309

    PubMed  Google Scholar 

  10. Brown MJ, Jenner DA, Allison DJ, Dollery CT (1981) Variations in individual organ release of noradrenaline measured by an improved radioenzymatic technique; limitations of peripheral venous measurements in the assessment of sympathetic nervous activity. Clin Sci 61:585–590

    PubMed  Google Scholar 

  11. Brush JE Jr, Eisenhofer G, Garty M, Stull R, Maron BJ, Cannon RO 3rd, Panza JA, Epstein SE, Goldstein DS (1989) Cardiac norepinephrine kinetics in hypertrophic cardiomyopathy. Circulation 79:836–844

    PubMed  Google Scholar 

  12. Calbet JA (2003) Chronic hypoxia increases blood pressure and noradrenaline spillover in healthy humans. J Physiol 551:379–386

    Article  PubMed  Google Scholar 

  13. Carlsson M, Carlsson A (1989) Effects of mild stress on adrenal and heart catecholamines in male and female rats. J Neural Transm 77:217–226

    Article  PubMed  Google Scholar 

  14. Chang PC, Kriek E, van der Krogt JA, van Brummelen P (1991) Does regional norepinephrine spillover represent local sympathetic activity? Hypertension 18:56–66

    PubMed  Google Scholar 

  15. Chang PC, van der Krogt JA, Vermeij P, van Brummelen P (1986) Norepinephrine removal and release in the fore-arm of healthy subjects. Hypertension 8:801–809

    PubMed  Google Scholar 

  16. Chidsey CA, Braunwald E, Morrow AG (1965) Catecholamine excretion and cardiac stores of norepinephrine in congestive heart failure. Am J Med 39:442–451

    Article  PubMed  Google Scholar 

  17. Cohen G, Holland B, Sha J, Goldenberg M (1959) Plasma concentrations of epinephrine and norepinephrine during intravenous infusions in man. J Clin Invest 38:1935–1941

    PubMed  Google Scholar 

  18. Coppack SW, Horowitz JF, Paramore DS, Cryer PE, Royal HD, Klein S (1998) Whole body, adipose tissue, and fore-arm norepinephrine kinetics in lean and obese women. Am J Physiol 275:E830–E834

    PubMed  Google Scholar 

  19. Cox HS, Kaye DM, Thompson JM, Turner AG, Jennings GL, Itsiopoulos C, Esler MD (1995) Regional sympathetic nervous activation after a large meal in humans. Clin Sci 89:145–154

    PubMed  Google Scholar 

  20. Dequattro V, Nagatsu T, Mendez A, Verska J (1973) Determinants of cardiac noradrenaline depletion in human congestive failure. Cardiovasc Res 7:344–350

    PubMed  Google Scholar 

  21. Eikelis N, Lambert G, Wiesner G, Kaye D, Schlaich M, Morris M, Hastings J, Socratous F, Esler M (2004) Extraadipocyte leptin release in human obesity and its relation to sympathoadrenal function. Am J Physiol Endocrinol Metab 286:E744–E752

    Article  PubMed  Google Scholar 

  22. Eisenhofer G (1994) Plasma normetanephrine for examination of extraneuronal uptake and metabolism of noradrenaline in rats. Naunyn Schmiedebergs Arch Pharmacol 349:259–269

    Article  PubMed  Google Scholar 

  23. Eisenhofer G (2001) The role of neuronal and extraneuronal plasma membrane transporters in the inactivation of peripheral catecholamines. Pharmacol Ther 91:35–62

    Article  PubMed  Google Scholar 

  24. Eisenhofer G, Åneman A, Friberg P, Hooper D, Fandriks L, Lonroth H, Hunyady B, Mezey E (1997) Substantial production of dopamine in the human gastrointestinal tract. J Clin Endocrinol Metab 82:3864–3871

    Article  PubMed  Google Scholar 

  25. Eisenhofer G, Åneman A, Hooper D, Rundqvist B, Friberg P (1996) Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans. J Neurochem 66:1565–1573

    PubMed  Google Scholar 

  26. Eisenhofer G, Coughtrie MW, Goldstein DS (1999) Dopamine sulphate: an enigma resolved. Clin Exp Pharmacol Physiol Suppl 26:S41–S53

    PubMed  Google Scholar 

  27. Eisenhofer G, Cox HS, Esler MD (1991) Noradrenaline reuptake and plasma dihydroxyphenylglycol during sustained changes in sympathetic activity in rabbits. J Auton Nerv Syst 32:217–231

    Article  PubMed  Google Scholar 

  28. Eisenhofer G, Cox HS, Esler MD (1990) Parallel increases in noradrenaline re-uptake and release into plasma during activation of the sympathetic nervous system in rabbits. Naunyn Schmiedebergs Arch Pharmacol 342:328–335

    Article  PubMed  Google Scholar 

  29. Eisenhofer G, Esler MD, Cox HS, Meredith IT, Jennings GL, Brush JE Jr, Goldstein DS (1990) Differences in the neuronal removal of circulating epinephrine and norepinephrine. J Clin Endocrinol Metab 70:1710–1720

    PubMed  Google Scholar 

  30. Eisenhofer G, Esler MD, Goldstein DS, Kopin IJ (1991) Neuronal uptake, metabolism, and release of tritiumlabeled norepinephrine during assessment of its plasma kinetics. Am J Physiol 261:E505–E515

    PubMed  Google Scholar 

  31. Eisenhofer G, Esler MD, Meredith IT, Dart A, Cannon RO 3rd, Quyyumi AA, Lambert G, Chin J, Jennings GL, Goldstein DS (1992) Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine. Circulation 85:1775–1785

    PubMed  Google Scholar 

  32. Eisenhofer G, Esler MD, Meredith IT, Ferrier C, Lambert G, Jennings G (1991) Neuronal re-uptake of noradrenaline by sympathetic nerves in humans. Clin Sci 80:257–263

    PubMed  Google Scholar 

  33. Eisenhofer G, Finberg JP (1994) Different metabolism of norepinephrine and epinephrine by catechol-O-methyltransferase and monoamine oxidase in rats. J Pharmacol Exp Ther 268:1242–1251

    PubMed  Google Scholar 

  34. Eisenhofer G, Friberg P, Rundqvist B, Quyyumi AA, Lambert G, Kaye DM, Kopin IJ, Goldstein DS, Esler MD (1996) Cardiac sympathetic nerve function in congestive heart failure. Circulation 93:1667–1676

    PubMed  Google Scholar 

  35. Eisenhofer G, Goldstein DS, Kopin IJ (1989) Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo. Clin Sci 76:171–182

    PubMed  Google Scholar 

  36. Eisenhofer G, Goldstein DS, Stull R, Ropchak TG, Keiser HR, Kopin IJ (1987) Dihydroxyphenylglycol and dihydroxymandelic acid during intravenous infusions of noradrenaline. Clin Sci 73:123–125

    PubMed  Google Scholar 

  37. Eisenhofer G, Kopin IJ, Goldstein DS (2004) Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacol Rev 56:331–349

    Article  PubMed  Google Scholar 

  38. Eisenhofer G, McCarty R, Pacak K, Russ H, Schömig E (1996) Disprocynium24, a novel inhibitor of the extraneuronal monoamine transporter, has potent effects on the inactivation of circulating noradrenaline and adrenaline in conscious rat. Naunyn Schmiedebergs Arch Pharmacol 354:287–294

    Article  PubMed  Google Scholar 

  39. Eisenhofer G, Rundquist B, Åneman A, Friberg P, Dakak N, Kopin IJ, Jacobs MC, Lenders JW (1995) Regional release and removal of catecholamines and extraneuronal metabolism to metanephrines. J Clin Endocrinol Metab 80:3009–3017

    Article  PubMed  Google Scholar 

  40. Eisenhofer G, Saigusa T, Esler MD, Cox HS, Angus JA, Dorward PK (1991) Central sympathoinhibition and peripheral neuronal uptake blockade after desipramine in rabbits. Am J Physiol 260:R824–R832

    PubMed  Google Scholar 

  41. Eisenhofer G, Smolich JJ, Cox HS, Esler MD (1991) Neuronal reuptake of norepinephrine and production of dihydroxyphenylglycol by cardiac sympathetic nerves in the anesthetized dog. Circulation 84:1354–1363

    PubMed  Google Scholar 

  42. Eisenhofer G, Smolich JJ, Esler MD (1992) Different desipramine-sensitive pulmonary removals of plasma epinephrine and norepinephrine in dogs. Am J Physiol 262:L360–L365

    PubMed  Google Scholar 

  43. Eisenhofer G, Smolich JJ, Esler MD (1992) Disposition of endogenous adrenaline compared to noradrenaline released by cardiac sympathetic nerves in the anaesthetized dog. Naunyn Schmiedebergs Arch Pharmacol 345:160–171

    Article  PubMed  Google Scholar 

  44. Esler M (1992) The autonomic nervous system and cardiac arrhythmias. Clin Auton Res 2:133–135

    Article  PubMed  Google Scholar 

  45. Esler M, Eisenhofer G, Chin J, Jennings G, Meredith I, Cox H, Lambert G, Thompson J, Dart A (1991) Is adrenaline released by sympathetic nerves in man? Clin Auton Res 1:103–108

    Article  PubMed  Google Scholar 

  46. Esler M, Eisenhofer G, Dart A, Chin J, Cox H, Lambert G, Jennings G (1991) Adrenaline release by the human heart. Clin Exp Pharmacol Physiol 18:67–70

    PubMed  Google Scholar 

  47. Esler M, Jackman G, Bobik A, Kelleher D, Jennings G, Leonard P, Skews H, Korner P (1979) Determination of norepinephrine apparent release rate and clearance in humans. Life Sci 25:1461–1470

    Article  PubMed  Google Scholar 

  48. Esler M, Jackman G, Kelleher D, Skews H, Jennings G, Bobik A, Korner P (1980) Norepinephrine kinetics in patients with idiopathic autonomic insufficiency. Circ Res 46:I47–I48

    PubMed  Google Scholar 

  49. Esler M, Jackman G, Leonard P, Bobik A, Skews H, Jennings G, Kelleher D, Korner P (1980) Determination of noradrenaline uptake, spillover to plasma and plasma concentration in patients with essential hypertension. Clin Sci 59(Suppl 6):311S–313S

    PubMed  Google Scholar 

  50. Esler M, Jackman G, Leonard P, Skews H, Bobik A, Jennings G (1981) Effect of propranolol on noradrenaline kinetics in patients with essential hypertension. Br J Clin Pharmacol 12:375–380

    PubMed  Google Scholar 

  51. Esler M, Jackman G, Leonard P, Skews H, Bobik A, Korner P (1981) Effect of norepinephrine uptake blockers on norepinephrine kinetics. Clin Pharmacol Ther 29:12–20

    PubMed  Google Scholar 

  52. Esler M, Jennings G, Korner P, Blombery P, Sacharias N, Leonard P (1984) Measurement of total and organ-specific norepinephrine kinetics in humans. Am J Physiol 247:E21–E28

    PubMed  Google Scholar 

  53. Esler M, Jennings G, Korner P, Willett I, Dudley F, Hasking G, Anderson W, Lambert G (1988) Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover. Hypertension 11:3–20

    PubMed  Google Scholar 

  54. Esler M, Jennings G, Lambert G (1989) Measurement of overall and cardiac norepinephrine release into plasma during cognitive challenge. Psychoneuroendocrinology 14:477–481

    Article  PubMed  Google Scholar 

  55. Esler M, Jennings G, Lambert G (1989) Noradrenaline release and the pathophysiology of primary human hypertension. Am J Hypertens 2:140S–146S

    PubMed  Google Scholar 

  56. Esler M, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G (1990) Overflow of catecholamine neurotransmitters to the circulation: source, fate, and functions. Physiol Rev 70:963–985

    PubMed  Google Scholar 

  57. Esler M, Kaye D, Lambert G, Esler D, Jennings G (1997) Adrenergic nervous system in heart failure. Am J Cardiol 80:7L–14L

    Article  PubMed  Google Scholar 

  58. Esler M, Kaye D, Thompson J, Jennings G, Cox H, Turner A, Lambert G, Seals D (1995) Effects of aging on epinephrine secretion and regional release of epinephrine from the human heart. J Clin Endocrinol Metab 80:435–442

    Article  PubMed  Google Scholar 

  59. Esler M, Lambert G, Brunner-La Rocca HP, Vaddadi G, Kaye D (2003) Sympathetic nerve activity and neurotransmitter release in humans: translation from pathophysiology into clinical practice. Acta Physiol Scand 177:275–284

    Article  PubMed  Google Scholar 

  60. Esler M, Skews H, Leonard P, Jackman G, Bobik A, Korner P (1981) Agedependence of noradrenaline kinetics in normal subjects. Clin Sci 60:217–219

    PubMed  Google Scholar 

  61. Esler MD, Turner AG, Kaye DM, Thompson JM, Kingwell BA, Morris M, Lambert GW, Jennings GL, Cox HS, Seals DR (1995) Aging effects on human sympathetic neuronal function. Am J Physiol 268:R278–R285

    PubMed  Google Scholar 

  62. Esler MD, Wallin G, Dorward PK, Eisenhofer G, Westerman R, Meredith I, Lambert G, Cox HS, Jennings G (1991) Effects of desipramine on sympathetic nerve firing and norepinephrine spillover to plasma in humans. Am J Physiol 260:R817–R823

    PubMed  Google Scholar 

  63. Floras JS (1992) Epinephrine and the genesis of hypertension. Hypertension 19:1–18

    PubMed  Google Scholar 

  64. Folkow B, Di Bona GF, Hjemdahl P, Toren PH, Wallin BG (1983) Measurements of plasma norepinephrine concentrations in human primary hypertension. A word of caution on their applicability for assessing neurogenic contributions. Hypertension 5:399–403

    PubMed  Google Scholar 

  65. Friberg P, Meredith I, Jennings G, Lambert G, Fazio V, Esler M (1990) Evidence for increased renal norepinephrine overflow during sodium restriction in humans. Hypertension 16:121–130

    PubMed  Google Scholar 

  66. Friedgen B, Wolfel R, Graefe KH (1996) The contribution by monoamine oxidase and catechol-O-methyltransferase to the total-body and pulmonary plasma clearance of catecholamines. Naunyn Schmiedebergs Arch Pharmacol 353:193–199

    Article  PubMed  Google Scholar 

  67. Friedgen B, Wolfel R, Russ H, Schömig E, Graefe KH (1996) The role of extraneuronal amine transport systems for the removal of extracellular catecholamines in the rabbit. Naunyn Schmiedebergs Arch Pharmacol 354:275–286

    Article  PubMed  Google Scholar 

  68. Goldstein DS, Brush JE Jr, Eisenhofer G, Stull R, Esler M (1988) In vivo measurement of neuronal uptake of norepinephrine in the human heart. Circulation 78:41–48

    PubMed  Google Scholar 

  69. Goldstein DS, Eisenhofer G, Sax FL, Keiser HR, Kopin IJ (1987) Plasma norepinephrine pharmacokinetics during mental challenge. Psychosom Med 49:591–605

    PubMed  Google Scholar 

  70. Goldstein DS, Golczynska A, Stuhlmuller J, Holmes C, Rea RF, Grossman E, Lenders J (1999) A test of the “epinephrine hypothesis” in humans. Hypertension 33:36–43

    PubMed  Google Scholar 

  71. Goldstein DS, Holmes C, Cannon RO 3rd, Eisenhofer G, Kopin IJ (1997) Sympathetic cardioneuropathy in dysautonomias. N Engl J Med 336:696–702

    Article  PubMed  Google Scholar 

  72. Goldstein DS, Holmes C, Frank SM, Dendi R, Cannon RO 3rd, Sharabi Y, Esler MD, Eisenhofer G (2002) Cardiac sympathetic dysautonomia in chronic orthostatic intolerance syndromes. Circulation 106:2358–2365

    Article  PubMed  Google Scholar 

  73. Goldstein DS, Holmes C, Li ST, Bruce S, Metman LV, Cannon RO 3rd (2000) Cardiac sympathetic denervation in Parkinson disease. Ann Intern Med 133:338–347

    PubMed  Google Scholar 

  74. Goldstein DS, Horwitz D, Keiser HR, Polinsky RJ, Kopin IJ (1983) Plasma l-[3H]norepinephrine, d-[14C]norepinephrine, and d,l-[3H]isoproterenol kinetics in essential hypertension. J Clin Invest 72:1748–1758

    PubMed  Google Scholar 

  75. Graefe KH, Henseling M (1983) Neuronal and extraneuronal uptake and metabolism of catecholamines. Gen Pharmacol 14:27–33

    PubMed  Google Scholar 

  76. Grossman E, Chang PC, Hoffman A, Tamrat M, Goldstein DS (1991) Evidence for functional alpha 2-adrenoceptors on vascular sympathetic nerve endings in the human forearm. Circ Res 69:887–897

    PubMed  Google Scholar 

  77. Grossman E, Chang PC, Hoffman A, Tamrat M, Kopin IJ, Goldstein DS (1991) Tracer norepinephrine kinetics: dependence on regional blood flow and the site of infusion. Am J Physiol 260:R946–R952

    PubMed  Google Scholar 

  78. Halbrügge T, Ungell AL, Wolfel R, Graefe KH (1988) Total body, systemic and pulmonary clearance and fractional extraction of unlabelled and differently 3H-labelled noradrenaline in the anaesthetized rabbit. Naunyn Schmiedebergs Arch Pharmacol 338:361–367

    PubMed  Google Scholar 

  79. Hasking GJ, Esler MD, Jennings GL, Burton D, Johns JA, Korner PI (1986) Norepinephrine spillover to plasma in patients with congestive heart failure: evidence of increased overall and cardiorenal sympathetic nervous activity. Circulation 73:615–621

    PubMed  Google Scholar 

  80. Hasking GJ, Esler MD, Jennings GL, Dewar E, Lambert G (1988) Norepinephrine spillover to plasma during steady-state supine bicycle exercise. Comparison of patients with congestive heart failure and normal subjects. Circulation 78:516–521

    PubMed  Google Scholar 

  81. Henriksen JH, Christensen NJ (1989) Plasma norepinephrine in humans: limitations in assessment of whole body norepinephrine kinetics and plasma clearance. Am J Physiol 257:E743–E750

    PubMed  Google Scholar 

  82. Henriksen JH, Ring-Larsen H, Christensen NJ (1987) Hepatic intestinal uptake and release of catecholamines in alcoholic cirrhosis. Evidence of enhanced hepatic intestinal sympathetic nervous activity. Gut 28:1637–1642

    PubMed  Google Scholar 

  83. Henry DP, Dentino M, Gibbs PS, Weinberger MH (1979) Vascular compart-mentalization of plasma norepinephrine in normal man: the relationships between venous and arterial norepinephrine concentration and the urinary excretion of norepinephrine. J Lab Clin Med 94:429–437

    PubMed  Google Scholar 

  84. Himura Y, Felten SY, Kashiki M, Lewandowski TJ, Delehanty JM, Liang CS (1993) Cardiac noradrenergic nerve terminal abnormalities in dogs with experimental congestive heart failure. Circulation 88:1299–1309

    PubMed  Google Scholar 

  85. Hjemdahl P, Fagius J, Freyschuss U, Wallin BG, Daleskog M, Bohlin G, Perski A (1989) Muscle sympathetic activity and norepinephrine release during mental challenge in humans. Am J Physiol 257:E654–E664

    PubMed  Google Scholar 

  86. Hoeldtke RD, Cilmi KM, Reichard GA, Jr., Boden G, Owen OE (1983) Assessment of norepinephrine secretion and production. J Lab Clin Med 101:772–782

    PubMed  Google Scholar 

  87. Ichinohe T, Igarashi O, Kaneko Y (1991) The influence of propranolol on the cardiovascular effects and plasma clearance of epinephrine. Anesth Prog 38:217–220

    PubMed  Google Scholar 

  88. Jacobs MC, Lenders JW, Willemsen JJ, Thien T (1997) Adrenomedullary secretion of epinephrine is increased in mild essential hypertension. Hypertension 29:1303–1308

    PubMed  Google Scholar 

  89. Johansson M, Rundqvist B, Eisenhofer G, Friberg P (1997) Cardiorenal epinephrine kinetics: evidence for neuronal release in the human heart. Am J Physiol 273:H2178–H2185

    PubMed  Google Scholar 

  90. Karlsson AK, Elam M, Lonnroth P, Sullivan L, Friberg P (1997) Differentiated norepinephrine spillover in human skeletal muscle. Am J Physiol 273:R16–R21

    PubMed  Google Scholar 

  91. Karlsson AK, Friberg P, Lonnroth P, Sullivan L, Elam M (1998) Regional sympathetic function in high spinal cord injury during mental stress and autonomic dysreflexia. Brain 121(Pt 9):1711–1719

    Article  PubMed  Google Scholar 

  92. Kaye D, Esler M (2005) Sympathetic neuronal regulation of the heart in aging and heart failure. Cardiovasc Res 66:256–264

    Article  PubMed  Google Scholar 

  93. Kaye DM, Lefkovits J, Cox H, Lambert G, Jennings G, Turner A, Esler MD (1995) Regional epinephrine kinetics in human heart failure: evidence for extra-adrenal, nonneural release. Am J Physiol 269:H182–H188

    PubMed  Google Scholar 

  94. Kaye DM, Lefkovits J, Jennings GL, Bergin P, Broughton A, Esler MD (1995) Adverse consequences of high sympathetic nervous activity in the failing human heart. J Am Coll Cardiol 26:1257–1263

    Article  PubMed  Google Scholar 

  95. Keeton TK, Biediger AM (1988) The measurement of norepinephrine clearance and spillover rate into plasma in conscious spontaneously hypertensive rats. Naunyn Schmiedebergs Arch Pharmacol 338:350–360

    PubMed  Google Scholar 

  96. Kennedy B, Ziegler MG (1991) Cardiac epinephrine synthesis. Regulation by a glucocorticoid. Circulation 84:891–895

    PubMed  Google Scholar 

  97. Kjeldsen SE, Westheim A, Aakesson I, Eide I, Leren P (1986) Plasma adrenaline and noradrenaline during orthostasis in man: the importance of arterial sampling. Scand J Clin Lab Invest 46:397–401

    PubMed  Google Scholar 

  98. Kopin IJ (1964) Storage and metabolism of catecholamines: the role of monoamine oxidase. Pharmacol Rev 16:179–191

    PubMed  Google Scholar 

  99. Kopin IJ, Gordon EK (1963) Origin of norepinephrine in the heart. Nature 199:1289

    Google Scholar 

  100. Kopin IJ, Rundqvist B, Friberg P, Lenders J, Goldstein DS, Eisenhofer G (1998) Different relationships of spillover to release of norepinephrine in human heart, kidneys, and forearm. Am J Physiol 275:R165–R173

    PubMed  Google Scholar 

  101. Lambert G, Naredi S, Eden E, Rydenhag B, Friberg P (2002) Sympathetic nervous activation following subarachnoid hemorrhage: Influence of intravenous clonidine. Acta Anaesthesiol Scand 46:160–165

    Article  PubMed  Google Scholar 

  102. Lameris TW, de Zeeuw S, Duncker DJ, Tietge W, Alberts G, Boomsma F, Verdouw PD, van den Meiracker AH (2002) Epinephrine in the heart: uptake and release, but no facilitation of norepinephrine release. Circulation 106:860–865

    Article  PubMed  Google Scholar 

  103. Landsberg L, Axelrod J (1968) Influence of pituitary, thyroid, and adrenal hormones on norepinephrine turnover and metabolism in the rat heart. Circ Res 22:559–571

    PubMed  Google Scholar 

  104. Lenders JW, Eisenhofer G, Armando I, Keiser HR, Goldstein DS, Kopin IJ (1993) Determination of metanephrines in plasma by liquid chromatography with electrochemical detection. Clin Chem 39:97–103

    PubMed  Google Scholar 

  105. Leuenberger U, Kenney G, Davis D, Clemson B, Zelis R (1992) Comparison of norepinephrine and isoproterenol clearance in congestive heart failure. Am J Physiol 263:H56–H60

    PubMed  Google Scholar 

  106. Leuenberger U, Sinoway L,Gubin S, Gaul L, Davis D, Zelis R (1993) Effects of exercise intensity and duration on norepinephrine spillover and clearance in humans. J Appl Physiol 75:668–674

    PubMed  Google Scholar 

  107. Liang CS, Fan TH, Sullebarger JT, Sakamoto S (1989) Decreased adrenergic neuronal uptake activity in experimental right heart failure. A chamber-specific contributor to beta-adrenoceptor downregulation. J Clin Invest 84:1267–1275

    PubMed  Google Scholar 

  108. Linares OA, Jacquez JA, Zech LA, Smith MJ, Sanfield JA, Morrow LA, Rosen SG, Halter JB (1987) Norepinephrine metabolism in humans. Kinetic analysis and model. J Clin Invest 80:1332–1341

    PubMed  Google Scholar 

  109. Lindqvist M, Melcher A, Hjemdahl P (1999) Flow dependence of forearm noradrenaline overflow, as assessed during mental stress and sodium nitroprusside infusion. J Hypertens 17:91–97

    PubMed  Google Scholar 

  110. Ludwig J, Halbrugge T, Vey G, Walter J, Graefe KH (1989) Haemodynamics as a determinant of the pharmacokinetics of and the plasma catecholamine responses to isoprenaline. Eur J Clin Pharmacol 37:493–500

    Article  PubMed  Google Scholar 

  111. Maas JW, Benensohn H, Landis DH (1970) A kinetic study of the disposition of circulating norepinephrine in normal male subjects. J Pharmacol Exp Ther 174:381–387

    PubMed  Google Scholar 

  112. Mansfield D, Kaye DM, Brunner La Rocca H, Solin P, Esler MD, Naughton MT (2003) Raised sympathetic nerve activity in heart failure and central sleep apnea is due to heart failure severity. Circulation 107:1396–1400

    Article  PubMed  Google Scholar 

  113. Marker JC, Cryer PE, Clutter WE (1994) Simplified measurement of norepinephrine kinetics: application to studies of aging and exercise training. Am J Physiol 267:E380–E387

    PubMed  Google Scholar 

  114. McCance AJ, Forfar JC (1989) Cardiac and whole body [3H]noradrenaline kinetics in ischaemic heart disease: contrast between unstable anginal syndromes and pacing induced ischaemia. Br Heart J 61:238–247

    PubMed  Google Scholar 

  115. McCance AJ, Thompson PA, Forfar JC (1993) Increased cardiac sympathetic nervous activity in patients with unstable coronary heart disease. Eur Heart J 14:751–757

    PubMed  Google Scholar 

  116. Medvedev OS, Esler MD, Angus JA, Cox HS, Eisenhofer G (1990) Simultaneous determination of plasma noradrenaline and adrenaline kinetics. Responses to nitroprussideinduced hypotension and 2-deoxyglucose-induced glucopenia in the rabbit. Naunyn Schmiedebergs Arch Pharmacol 341:192–199

    Article  PubMed  Google Scholar 

  117. Meredith IT, Eisenhofer G, Lambert GW, Dewar EM, Jennings GL, Esler MD (1993) Cardiac sympathetic nervous activity in congestive heart failure. Evidence for increased neuronal norepinephrine release and preserved neuronal uptake. Circulation 88:136–145

    PubMed  Google Scholar 

  118. Meredith IT, Eisenhofer G, Lambert GW, Jennings GL, Thompson J, Esler MD (1992) Plasma norepinephrine responses to head-up tilt are misleading in autonomic failure. Hypertension 19:628–633

    PubMed  Google Scholar 

  119. Meredith IT, Esler MD, Cox HS, Lambert GW, Jennings GL, Eisenhofer G (1991) Biochemical evidence of sympathetic denervation of the heart in pure autonomic failure. Clin Auton Res 1:187–194

    Article  PubMed  Google Scholar 

  120. Merlet P, Dubois-Rande JL, Adnot S, Bourguignon MH, Benvenuti C, Loisance D, Valette H, Castaigne A, Syrota A (1992) Myocardial beta-adrenergic desensitization and neuronal norepinephrine uptake function in idiopathic dilated cardiomyopathy. J Cardiovasc Pharmacol 19:10–16

    PubMed  Google Scholar 

  121. Naredi S, Lambert G, Eden E, Zall S, Runnerstam M, Rydenhag B, Friberg P (2000) Increased sympathetic nervous activity in patients with nontraumatic subarachnoid hemorrhage. Stroke 31:901–906

    PubMed  Google Scholar 

  122. Neri Serneri GG, Boddi M, Arata L, Rostagno C, Dabizzi P, Coppo M, Bini M, Lazzerini S, Dagianti A, Gensini GF (1993) Silent ischemia in unstable angina is related to an altered cardiac norepinephrine handling. Circulation 87:1928–1937

    PubMed  Google Scholar 

  123. Norrsell H, Eliasson T, Mannheimer C, Augustinsson LE, Bergh CH, Andersson B, Waagstein F, Friberg P (1997) Effects of pacing-induced myocardial stress and spinal cord stimulation on whole body and cardiac norepinephrine spillover. Eur Heart J 18:1890–1896

    PubMed  Google Scholar 

  124. Packer M, Bristow MR, Cohn JN, Colucci WS, Fowler MB, Gilbert EM, Shusterman NH (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. US, Carvedilol Heart Failure Study Group. N Engl J Med 334:1349–1355

    Article  PubMed  Google Scholar 

  125. Patel JN, Eisenhofer G, Coppack SW, Miles JM (1999) Norepinephrine spillover in forearm and subcutaneous adipose tissue before and after eating. J Clin Endocrinol Metab 84:2815–2819

    Article  PubMed  Google Scholar 

  126. Peronnet F, Beliveau L, Boudreau G, Trudeau F, Brisson G, Nadeau R (1988) Regional plasma catecholamine removal and release at rest and exercise in dogs. Am J Physiol 254:R663–R672

    PubMed  Google Scholar 

  127. Peterson RE, Wyngaarden JB, Guerra SL, Brodie BB, Bunim JJ (1955) The physiological disposition and metabolic fate of hydrocortisone in man. J Clin Invest 34:1779–1794

    PubMed  Google Scholar 

  128. Petersson MJ, Rundqvist B, Johansson M, Eisenhofer G, Lambert G, Herlitz H, Jensen G, Friberg P (2002) Increased cardiac sympathetic drive in renovascular hypertension. J Hypertens 20:1181–1187

    Article  PubMed  Google Scholar 

  129. Pool PE, Covell JW, Levitt M, Gibb J, Braunwald E (1967) Reduction of cardiac tyrosine hydroxylase activity in experimental congestive heart failure. Its role in the depletion of cardiac norepinephrine stores. Circ Res 20:349–353

    PubMed  Google Scholar 

  130. Potter JF, Fotherby MD, Macdonald IA (1993) Repeatability and relationship between arterialized catecholamines and blood pressure in elderly subjects. Age Ageing 22:404–410

    PubMed  Google Scholar 

  131. Rittenberg D, Foster GL (1940) A new procedure for quantitative analysis by isotope dilution,with application to the determination of amino acids and fatty acids. J Biol Chem 133:737–744

    Google Scholar 

  132. Rongen GA, Lenders JW, Lambrou J, Willemsen JJ, Van Belle H, Thien T, Smits P (1996) Presynaptic inhibition of norepinephrine release from sympathetic nerve endings by endogenous adenosine. Hypertension 27:933–938

    PubMed  Google Scholar 

  133. Rongen GA, Lenders JW, Smits P, Floras JS (2000) Comparison of two indices for forearm noradrenaline release in humans. Clin Sci (Lond) 99:363–369

    Article  PubMed  Google Scholar 

  134. Rose CP, Burgess JH, Cousineau D (1985) Tracer norepinephrine kinetics in coronary circulation of patients with heart failure secondary to chronic pressure and volume overload. J Clin Invest 76:1740–1747

    PubMed  Google Scholar 

  135. Rumantir MS, Jennings GL, Lambert GW, Kaye DM, Seals DR, Esler MD (2000) The ‘adrenaline hypothesis’ of hypertension revisited: evidence for adrenaline release from the heart of patients with essential hypertension. J Hypertens 18:717–723

    Article  PubMed  Google Scholar 

  136. Rundqvist B, Elam M, Bergmann-Sverrisdottir Y, Eisenhofer G, Friberg P (1997) Increased cardiac adrenergic drive precedes generalized sympathetic activation in human heart failure. Circulation 95:169–175

    PubMed  Google Scholar 

  137. Schlaich MP, Lambert E, Kaye DM, Krozowski Z, Campbell DJ, Lambert G, Hastings J, Aggarwal A, Esler MD (2004) Sympathetic augmentation in hypertension: role of nerve firing, norepinephrine reuptake, and Angiotensin neuromodulation. Hypertension 43:169–175

    Article  PubMed  Google Scholar 

  138. Seals DR, Esler MD (2000) Human ageing and the sympathoadrenal system. J Physiol 528:407–417

    Article  PubMed  Google Scholar 

  139. Smolich JJ, Cox HS, Berger PJ, Walker AM, Eisenhofer G, Esler MD (1997) Left ventricular norepinephrine and epinephrine kinetics at birth in lambs. Circ Res 81:438–447

    PubMed  Google Scholar 

  140. Sole MJ, Helke CJ, Jacobowitz DM (1982) Increased dopamine in the failing hamster heart: transvesicular transport of dopamine limits the rate of norepinephrine synthesis. Am J Cardiol 49:1682–1690

    Article  PubMed  Google Scholar 

  141. Stein M, Deegan R, He H, Wood AJ (1993) Beta-adrenergic receptor-mediated release of norepinephrine in the human forearm. Clin Pharmacol Ther 54:58–64

    PubMed  Google Scholar 

  142. Stromblad BC, Nickerson M (1961) Accumulation of epinephrine and norepinephrine by some rat tissues. J Pharmacol Exp Ther 134:154–159

    PubMed  Google Scholar 

  143. Vaz M, Cox HS, Kaye DM, Turner AG, Jennings GL, Esler MD (1995) Fallibility of plasma noradrenaline measurements in studying postprandial sympathetic nervous responses. J Auton Nerv Syst 56:97–104

    Article  PubMed  Google Scholar 

  144. Vaz M, Jennings G, Turner A, Cox H, Lambert G, Esler M (1997) Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation 96:3423–3429

    PubMed  Google Scholar 

  145. Wilkinson DJ, Thompson JM, Lambert GW, Jennings GL, Schwarz RG, Jefferys D, Turner AG, Esler MD (1998) Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Arch Gen Psychiatry 55:511–520

    Article  PubMed  Google Scholar 

  146. Ziegler MG, Chernow B, Woodson LC, Coyle J, Cruess D, Lake CR (1986) The effect of propranolol on catecholamine clearance. Clin Pharmacol Ther 40:116–119

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda (MD), USA

    Graeme Eisenhofer PhD

  2. Building 10, Room 6N252, National Institutes of Health, Bethesda (MD) 20892, USA

    Graeme Eisenhofer PhD

Authors
  1. Graeme Eisenhofer PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Graeme Eisenhofer PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eisenhofer, G. Sympathetic nerve function. Clin Auton Res 15, 264–283 (2005). https://doi.org/10.1007/s10286-005-0292-5

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10286-005-0292-5

Key words

Search

Navigation