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Central nervous system norepinephrine metabolism in hypertension

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Abstract

Although the pivotal role played by the brain in the maintenance of optimal physiologic and psychologic health has long been recognized, methods for the direct examination of human central nervous system processes have only recently been developed. A growing body of evidence indicates that central nervous systemmonoaminergic cell groups, in particular those utilizing norepinephrine as their neurotransmitter, participate in the excitatory regulation of the sympathetic nervous system and the development of the hypertensive state.

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References and Recommended Reading

  1. Korner PI: Circulatory control and the supercontrollers. J Hypertens 1995, 13:1508–1521.

    Article  PubMed  CAS  Google Scholar 

  2. Reid CM, Dart AM, Dewar EM, Jennings GL: Interactions between the effects of exercise and weight loss on risk factors, cardiovascular hemodynamics and left ventricular structure in overweight subjects. J Hypertens 1994, 12:291–301.

    PubMed  CAS  Google Scholar 

  3. Bjorklund A, Lindvall O: Handbook of Chemical Neuroanatomy. Amsterdam: Elsevier; 1985.

    Google Scholar 

  4. Hokfelt T, Johansson O, Goldstein M: Chemical anatomy of the brain. Science 1984, 225:1326–1334.

    Article  PubMed  CAS  Google Scholar 

  5. Foote SL, Bloom FE, Aston-Jones G: Nucleus locus ceruleus: new evidence of anatomical and physiological specificity. Physiol Rev 1983, 63:844–914.

    PubMed  CAS  Google Scholar 

  6. Ferrier C, Esler MD, Eisenhofer G, et al.: Increased norepinephrine spillover into the jugular veins in essential hypertension. Hypertension 1992, 19:62–69.

    PubMed  CAS  Google Scholar 

  7. Lambert GW, Ferrier C, Kaye DM, et al.: Central nervous system norepinephrine turnover in essential hypertension. Ann N Y Acad Sci 1995, 763:679–694.

    Article  PubMed  CAS  Google Scholar 

  8. Lambert GW, Thompson JM, Turner AG, et al.: Cerebral noradrenaline spillover and its relation to muscle sympathetic nervous activity in healthy human subjects. J Auton Nerv Syst 1997, 64:57–64.

    Article  PubMed  CAS  Google Scholar 

  9. Ferrier C, Jennings GL, Eisenhofer G, et al.: Evidence for increased noradrenaline release from subcortical brain regions in essential hypertension. J Hypertens 1993, 11:1217–1227.

    Article  PubMed  CAS  Google Scholar 

  10. Chalmers J, Pilowsky P: Brainstem and bulbospinal neurotransmitter systems in the control of blood pressure. J Hypertens 1991, 9:675–694.

    Article  PubMed  CAS  Google Scholar 

  11. Kopin IJ: Catecholamine metabolism: basic aspects and clinical significance. Pharmacol Rev 1985, 37:333–364.

    PubMed  CAS  Google Scholar 

  12. Goldstein DS, Eisenhofer G, Stull R, et al.: Plasma dihydroxyphenylglycol and the intraneuronal disposition of norepinephrine in humans. J Clin Invest 1988, 81:213–220.

    PubMed  CAS  Google Scholar 

  13. Lambert GW, Kaye DM, Vaz M, et al.: Regional origins of 3-methoxy-4-hydroxyphenylglycol in plasma: effects of chronic sympathetic nervous activation and denervation, and acute reflex sympathetic stimulation. J Auton Nerv Syst 1995, 55:169–178.

    Article  PubMed  CAS  Google Scholar 

  14. Maas JW, Hattox SE, Landis DH, Roth RH: A direct method for studying 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) production by brain in awake animals. Eur J Pharmacol 1977, 46:221–228.

    Article  PubMed  CAS  Google Scholar 

  15. DeMet EM, Halaris AE: Origin and distribution of 3-methoxy-4-hydroxyphenylglycol in body fluids. Biochem Pharmacol 1979, 28:3043–3050.

    Article  PubMed  CAS  Google Scholar 

  16. Blombery PA, Kopin IJ, Gordon EK, et al.: Conversion of MHPG to vanillymandelic acid: implications for the importance of urinary MHPG. Arch Gen Psychiatry 1980, 37:1095–1098.

    PubMed  CAS  Google Scholar 

  17. Kopin IJ, Blombery P, Ebert MH, et al.: Disposition and metabolism of MHPG-CD3 in humans: plasma MHPG as the principal pathway of norepinephrine metabolism and as an important determinant of CSF levels of MHPG. In Frontiers in Biochemical and Pharmacological Research in Depression. Edited by Usdin E. New York: Raven Press; 1984:57–68.

    Google Scholar 

  18. Lambert GW, Eisenhofer G, Cox HS, et al.: Direct determination of homovanillic acid release from the human brain, an indicator of central dopaminergic activity. Life Sci 1991, 49:1061–1072.

    Article  PubMed  CAS  Google Scholar 

  19. Gray H: Angiology and neurology. In Gray’s Anatomy, edn 36. Edited by Williams PL, Warwick R. Edinburgh: Churchill Livingston; 1980:738–751.

    Google Scholar 

  20. Lambert GW, Vaz M, Rajkumar C, et al.: Cerebral metabolism and its relationship with sympathetic nervous activity in essential hypertension: evaluation of the Dickinson hypothesis. J Hypertens 1996, 14:951–959.

    Article  PubMed  CAS  Google Scholar 

  21. Lambert GW, Kaye DM, Thompson JM, et al.: Internal jugular venous spillover of noradrenaline and metabolites and their association with sympathetic nervous activity. Acta Physiol Scand 1998, 163:155–163.

    Article  PubMed  CAS  Google Scholar 

  22. Eide I, Kolloch R, DeQuattro V, et al.: Raised cerebrospinal fluid norepinephrine in some patients with primary hypertension. Hypertension 1979, 1:255–260.

    PubMed  CAS  Google Scholar 

  23. Ziegler MG, Lake CR, Wood JH, Brooks BR: Relationship between cerebrospinal fluid norepinephrine and blood pressure in neurologic patients. Clin Exp Hypertens 1980, 2:995–1008.

    PubMed  CAS  Google Scholar 

  24. Lambert GW, Ferrier C, Kaye DM, et al.: Monoaminergic neuronal activity in subcortical brain regions in essential hypertension. Blood Press 1994, 3:55–66.

    PubMed  CAS  Google Scholar 

  25. Palkovits M: Neuropeptides and Biogenic Amines in Central Cardiovascular Control Mechanisms. New York: Raven; 1981.

    Google Scholar 

  26. Van Huysse JW, Bealer SL: Central nervous system norepinephrine release during hypotension and hyperosmolality in conscious rats. Am J Physiol 1991, 260:R1071-R1076.

    PubMed  Google Scholar 

  27. Huangfu D, Koshiya N, Guyenet P: A5 noradrenergic unit activity and sympathetic nerve discharge in rats. Am J Physiol 1991, 261:R393-R402.

    PubMed  CAS  Google Scholar 

  28. Singewald S, Philippu A: Catecholamine release in the locus coeruleus is modified by experimentally induced changes in hemodynamics. Naunyn Schmiedebergs Arch Pharmacol 1993, 347:21–27.

    PubMed  CAS  Google Scholar 

  29. Pacak K, Yadid G, Jakab G, et al.: In vivo hypothalamic release and synthesis of catecholamines in spontaneously hypertensive rats. Hypertension 1993, 22:467–478.

    PubMed  CAS  Google Scholar 

  30. Qualy JM, Westfall TC: Age-dependent overflow of endogenous norepinephrine from paraventricular hypothalamic nucleus of hypertensive rats. Am J Physiol 1993, 265:H39-H46.

    PubMed  CAS  Google Scholar 

  31. Elam M, Svensson TH, Thoren P: Differentiated cardiovascular afferent regulation of locus coeruleus and sympathetic nerves. Brain Res 1985, 358:77–84.

    Article  PubMed  CAS  Google Scholar 

  32. Esler M, Julius S, Zweifler A, et al.: Mild high-renin essential hypertension: a neurogenic human hypertension? N Engl J Med 1977, 296:405–411.

    Article  PubMed  CAS  Google Scholar 

  33. Fujishima M, Ibayashi S, Fujii K, Mori S: Cerebral blood flow and brain function in hypertension. Hypertens Res 1995, 18:111–117.

    PubMed  CAS  Google Scholar 

  34. Waldstein SR, Manuck SB, Ryan CM, Muldoon MF: Neuropsychological correlates of hypertension: review and methodological considerations. Psychol Bull 1991, 110:451–468.

    Article  PubMed  CAS  Google Scholar 

  35. Vaz M, Jennings G, Turner A, et al.: Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation 1997, 96:3423–3429. Documentation that important regional alterations in sympathetic nervous activity occur in the absence of changes in global indices of sympathetic nervous function in obese individuals. The observation that renal norepinephrine spillover is enhanced in obesity may have implications for the development of hypertension in this group.

    PubMed  CAS  Google Scholar 

  36. Rumantir MS, Vaz M, Jennings GL, et al.: Neural mechanisms in human obesity-related hypertension. J Hypertens 1999, 17:1125–1133.

    Article  PubMed  CAS  Google Scholar 

  37. Lambert GW, Jonsdottir IH: Influence of voluntary exercise on hypothalamic norepinephrine. J Appl Physiol 1998, 85:962–966.

    PubMed  CAS  Google Scholar 

  38. Lambert GW, Vaz M, Cox HS, et al.: Human obesity is associated with a chronic elevation in brain 5-hydroxytryptamine turnover. Clin Sci (Colch) 1999, 96:191–197. Clinical investigation noting that in human obesity, in the face of a chronic elevation in peripheral satiety signals, brain serotonergic processes are switched on accordingly, but the subsequent physiologic response involving a reduction in food intake, increased thermogenesis, and sympathetic activity is in some way impeded.

    Article  CAS  Google Scholar 

  39. Bray GA, York DA, Fisler JS: Experimental obesity: a homeostatic failure due to defective nutrient stimulation of the sympathetic nervous system. Vitam Horm 1989, 45:1–125.

    Article  PubMed  CAS  Google Scholar 

  40. Spraul M, Ravussin E, Fontvielle AM, et al.: Reduced sympathetic nervous activity. A potential mechanism predisposing to body weight gain. J Clin Invest 1993, 92:1730–1735.

    PubMed  CAS  Google Scholar 

  41. Wiesner G, Vaz M, Collier G, et al.: Leptin is released from the human brain: influence of adiposity and gender. J Clin Endocrinol Metab 1999, 84:2270–2274. Demonstration of leptin release from the human brain, the clinical significance of which remains to be seen.

    Article  PubMed  CAS  Google Scholar 

  42. Nelson L, Jennings GL, Esler MD, Korner PI: The effect of changing levels of physical activity on blood pressure and haemodynamics in patients with essential hypertension. Lancet 1986, 2:473–476.

    Article  PubMed  CAS  Google Scholar 

  43. Paffenbarger RS, Hyde RT, Wing AL, Hsien CC: Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med 1986, 314:605–613.

    Article  PubMed  Google Scholar 

  44. Zheng D, Wooter MH, Zhou Q, Dohm GL: The effect of exercise on ob gene expression. Biochem Biophys Res Commun 1996, 225:747–750.

    Article  PubMed  CAS  Google Scholar 

  45. Friedman JE, Ferrara CM, Aulak KS, et al.: Exercise training down-regulates ob gene expression in the genetically obese SHHF/Mcc-fa(cp) rat. Horm Metab Res 1997, 29:214–219.

    Article  PubMed  CAS  Google Scholar 

  46. Kannan H, Hayashida Y, Yamashita H: Increase in sympathetic outflow by paraventricular nucleus stimulation in awake rats. Am J Physiol 1989, 256:R1325-R1330.

    PubMed  CAS  Google Scholar 

  47. Woo N, Mukherjee K, Ganguly PK: Norepinephrine levels in paraventricular nucleus of spontaneously hypertensive rats: a role of neuropeptide Y. Am J Physiol 1993, 265:H893-H898.

    PubMed  CAS  Google Scholar 

  48. Johansson M, Elam M, Rundqvist B, et al.: Increased sympathetic nerve activity in renovascular hypertension. Circulation 1999, 99:2537–2542. Unequivocal demonstration that sympathetic nervous activity is elevated in renovascular hypertension.

    PubMed  CAS  Google Scholar 

  49. Guyenet PG: Is the hypotensive effect of clonidine and related drugs due to imidazoline binding sites? Am J Physiol 1997, 273:R1580-R1584.

    PubMed  CAS  Google Scholar 

  50. Makaritsis KP, Johns C, Gavras I, et al.: Sympathoinhibitory function of the alpha(2A)-adrenergic receptor subtype. Hypertension 1999, 34:403–407.

    PubMed  CAS  Google Scholar 

  51. Naraghi R, Gaab MR, Walter GF, Kleinberg B: Arterial hypertension and neurovascular compression at the ventrolateral medull: a comparative microanatomical and pathological study. J Neurosurg 1992, 77:102–112.

    Google Scholar 

  52. Morimoto S, Sasaki S, Itoh H, et al.: Sympathetic activation and contribution of genetic factors in hypertension with neurovascular compression of the rostral ventrolateral medulla. J Hypertens 1999, 17:1577–1582.

    Article  PubMed  CAS  Google Scholar 

  53. Jannetta PJ, Segal R, Wolfson SK Jr: Neurogenic hypertension: etiology and surgical treatment I: observations in 53 patients. Ann Surg 1985, 201:391–398.

    Article  PubMed  CAS  Google Scholar 

  54. Morimoto S, Sasaki S, Takeda K, et al.: Decreases in blood pressure and sympathetic nerve activity by microvascular decompression of the rostral ventrolateral medulla in essential hypertension. Stroke 1999, 30:1707–1710. Intriguing case report suggesting that hypertension accompanying microvascular compression occurs as a result of activation of the sympathetic nervous system.

    PubMed  CAS  Google Scholar 

  55. Dampney RA: Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 1994, 74:323–364.

    PubMed  CAS  Google Scholar 

  56. Reis DJ, Ruggiero DA, Morrison SF: The C1 area of the rostral ventrolateral medulla oblongata. A critical brainstem region for control of resting and reflex integration of arterial pressure. Am J Hypertens 1989, 2:363S-374S.

    PubMed  CAS  Google Scholar 

  57. Lambert GW, Kaye DM, Lefkovits J, et al.: Increased central nervous system monoamine neurotransmitter turnover and its association with sympathetic nervous activity in treated heart failure patients. Circulation 1995, 92:1813–1818.

    PubMed  CAS  Google Scholar 

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  1. Human Neurotransmitters Laboratory, Baker Medical Research Institute, St. Kilda Road Central, PO Box 6492, 8008, Melbourne, Victoria, Australia

    Gavin W. Lambert PhD

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  1. Gavin W. Lambert PhD
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Lambert, G.W. Central nervous system norepinephrine metabolism in hypertension. Current Science Inc 2, 302–310 (2000). https://doi.org/10.1007/s11906-000-0014-2

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