Skip to main content
Log in

Abnormal suppression of arginine-vasopressin by clonidine in multiple system atrophy

  • Research Paper
  • Published:
Clinical Autonomic Research Aims and scope Submit manuscript

Abstract

In normal man, the centrally activeα 2-adrenoceptor agonist clonidine reduces arginine-vasopressin (AVP) secretion, probably by presynaptic inhibition of noradrenergic neuron terminals in the supraoptic nucleus. A lesion of noradrenergic pathways in animals abolishes this response to clonidine. At postmortem in multiple system atrophy (MSA) there is marked loss of hypothalamic noradrenergic innervation. We hypothesized that the AVP response to clonidine in MSA may be abnormal and therefore studied the AVP response to clonidine (2μg/kg iv) in 10 subjects with MSA and compared them to six healthy age-matched control subjects. Basal levels of AVP were similar in controls and MSA. Following clonidine there was a significantly greater fall in controls than MSA (−47±4% vs −25±6%; p<0.05). There was a similar fall in mean arterial pressure (MAP) and plasma catecholamines in both groups, with no change in plasma osmolarity, excluding these as a contributary factor. In conclusion, there is an abnormal AVP response to clonidine in MSA, which probably represents loss of functional noradrenergic innervation of the supraoptic nucleus.

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

Access this article

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. Sawchenko P, Swanson L. The organisation of noradrenergic pathways from the brainstem to the paraventricular and supraoptic nuclei in the rat.Brain Res Rev 1982; 4:275–325.

    Article  Google Scholar 

  2. Day T and Renaud L. Electrophysiological evidence that noradrenergic afferents selectively facilitate the activity of supraoptic neurones.Brain Res 1984; 303:233–240.

    Article  CAS  PubMed  Google Scholar 

  3. Harris M, Loewy A. Neural regulation of vasopressin containing hypothalamic neurones and the role of vasopressin in cardiovascular function. In;Central regulation of autonomic functions. Eds Loewy A, Spyer K. Oxford University Press (Oxford) 1990: 224–246.

    Google Scholar 

  4. Willoughby J, Jervois P, Menadue M, Blessing W. Noradrenaline by action of α1-adrenoceptors in the region of the supraoptic nucleus causes secretion of AVP in the unanaesthetised rat.Neuroendocrinology 1987; 45:219–226.

    Article  CAS  PubMed  Google Scholar 

  5. Reid I, Nolan P, Wolf J, Keil L. Suppression of vasopressin secretion by clonidine: effects of α-adrenoceptor antagonists.Endocrinology 1979; 104:1403–6.

    Article  CAS  PubMed  Google Scholar 

  6. Kimura T, Share L, Wang B, Crofton J. The role of central adrenoceptors in the control of vasopressin release and BP.Endocrinology 1981; 108:1829–36.

    Article  CAS  PubMed  Google Scholar 

  7. Sved A. Clonidine can lower BP by inhibiting vasopressin release.Eur J Pharm 1985; 109:111–16.

    Article  CAS  Google Scholar 

  8. Peskind E, Raskind M, Leake R, Ervin M, Ross M, Dorsa D. Clonidine decreases plasma and cerebrospinal fluid AVP but not oxytocin in humans.Neuroendocrinology 1987; 46:395–400.

    Article  CAS  PubMed  Google Scholar 

  9. Brown G, Mazurek, Allen D, Szechman R, Cleghom J. Dose response profiles of plasma GH and vasopressin after clonidine challenge in man.Psychiatry Res 1990; 31:311–320.

    Article  CAS  PubMed  Google Scholar 

  10. Kimber J, Watson L, Mathias C. Distinction of IPD from MSA by stimulation of GH release with clonidine.Lancet 1997; 349:1877–81.

    Article  CAS  PubMed  Google Scholar 

  11. Mathias C, Williams A. The Shy-Drager syndrome (and multiple system atrophy). In:Neurodegenerative diseases. Calne D, ed. Philadelphia: W.B. Saunders; 1994:743–67.

    Google Scholar 

  12. Mathias C. Disorders of the autonomic nervous system. In:Neurology in clinical practice. Bradley W, Daroff R, Fenichel G, Marsden C, eds. Philadelphia: Butterworth-Heinemann; 1997:1661–86.

    Google Scholar 

  13. May C, Ham I, Heslop K, Stone F, Mathias C. Intravenous morphine causes hypotension, hypoglycaemia and increases sympatho-adrenal acivity in the conscious rat.Clin Sci 1988; 75:71–7.

    Article  CAS  PubMed  Google Scholar 

  14. Williams T, Lightman S, Bannister R. Vasopressin secretion in progressive autonomic failure: evidence for defective afferent cardiovascular pathways.J Neurol Neurosurg Psychiatry 1985; 48:225–228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Shy G, Drager G. A neurologic syndrome associated with orthostatic hypotension.Arch Neurol 1960; 2:511–27.

    Article  CAS  PubMed  Google Scholar 

  16. Takahashi A, Takagi S, Yamamoto K, Yamada T. Shy-Drager syndrome—its correlation with olivo-ponto-cerebellar atrophy.Clin Neurol (Japan). 1969; 9:121–9.

    Google Scholar 

  17. Lockwood A. Shy-Drager syndrome with abnormal respirations and arginine-vasopressin release.Arch Neurol 1976; 33:292–94.

    Article  CAS  PubMed  Google Scholar 

  18. Ozawa T, Oyanagi K, Tanaka H, Horikawa Y, Takahashi H, Morita T, Tsuji S. Suprachiasmatic nucleus in a patient with MSA with abnormal circadian rhythm of arginine-vasopressin into plasma.J Neurol Sci 1988; 154:116–121.

    Article  Google Scholar 

  19. Ansorge O, Daniel S, Pearce R. Neuronal loss and plasticity in the supraoptic nucleus in PD.Neurology 1997; 49:610–13.

    Article  CAS  PubMed  Google Scholar 

  20. Zerbe R, Henry D, Robertson G. Vasopressin response to orthostatic hypotension; etiologic and clinical implications.Am J Med 1983; 74:271.

    Article  Google Scholar 

  21. Puritz R, Lightman S, Wilcox C, Forsling M, Bannister R. Blood pressure and vasopressin in progressive autonomic failure.Brain 1983; 106:503–511.

    Article  PubMed  Google Scholar 

  22. Kauffmann H, Oribe E, Miller M, Knott P, Wiltshire-Clement, Yahr M. Hypotension induced vasopressin release distinguishes between PAF and MSA.Neurology 1992; 42:590–593.

    Article  Google Scholar 

  23. Reid W, Ewing D, Lightman S, Eadington D, Williams T, Roulston J, Clarke B. Vasopressin secretion in diabetic subjects with and without autonomic neuropathy: responses to osmotic and postural stimulation.Clin Sci 1989; 77:589–97.

    Article  CAS  PubMed  Google Scholar 

  24. Poole C, Williams T, Lightman S, Frankel H. Neuroendocrine control of vasopressin secretion and its effect on BP in patients with spinal cord transection.Brain 1987; 110:727–35.

    Article  PubMed  Google Scholar 

  25. Wall B, Runyan K, Williams H, Bobal M, Crofton J, Share L, Cooke R. Characteristics of vasopressin release during controlled reduction in MAP.J Lab Clin Med 1994; 124:554–63.

    CAS  PubMed  Google Scholar 

  26. Thomaides T, Ray Chaudhuri K, Maule S, Watson L, Marsden C, Mathias C. Growth hormone reponse to clonidine in central and peripheral primary autonomic failure.Lancet 1992; 340:263–66.

    Article  CAS  PubMed  Google Scholar 

  27. Kooner J, Birch R, Frankel H, Peart W, Mathias C. Heamodynamic and neurohormonal effects of clonidine in patients with pre and post ganglionic sympathetic lesions. Evidence for a central sympatholytic action.Circulation 1991; 84:75–83.

    Article  CAS  PubMed  Google Scholar 

  28. Thomaides T, Ray Chaudhuri K, Maule S, Mathias C. Differential responses in superior mesenteric artery flow may expalin the variant pressor responses to clonidine in two groups with autonomic failure.Clin Sci 1992; 83:59–64.

    Article  CAS  PubMed  Google Scholar 

  29. Schmitt H, Schmitt H, Boisser J, Giudicelli J. Centrally mediated decrease in sympathetic tone induced by 2-(2,3-dichlorophenylamino)-2-imidazoline.Eur J Pharmacol 1967; 2:147–148.

    Article  CAS  PubMed  Google Scholar 

  30. Pouttu J, Scheinin B, Rosenberg P, Vinamaki O, Scheinin M. Oral premedication with clonidine; effects on stress responses during general anaesthesia.Acta Anaesthesiologica Scand 1987; 31:730–4.

    Article  CAS  Google Scholar 

  31. Sone H, Okuda Y, Bannai C et al. Syndrome of innappropriate ADH secretion and Gerhardt's syndrome associated with Shy-Drager syndrome.Intern Med 1994; 33:773–8.

    Article  CAS  PubMed  Google Scholar 

  32. Saper C, Loewy A, Swanson L, Cowan W. Direct hypothalamoautonomic connections.Brain Res 1976; 117:305–12.

    Article  CAS  PubMed  Google Scholar 

  33. Moore Y. The innervation of the mammalian pineal gland. In:The pineal and reproduction. Reiter R, Karger S, eds. Basel; 1978:1–29.

  34. Tetsuo M, Polinsky R, Markey S, Kopin I. Urinary 6-hydroxymelatonin excretion in patients with orthostatic hypotension.J Clin Endoc Metab 1981; 53:607–10.

    Article  CAS  Google Scholar 

  35. Zerbe R, Palcovits M. Changes in vasopressin content of discrete brain regions in response to stimuli for vasopressin secretion.Neuroendocrinology 1984; 38:285–9.

    Article  CAS  PubMed  Google Scholar 

  36. Khanna S, Sibbald J, Day T.α 2-adrenergic modulation of A1 noradrenergic neurone input to supraoptic vasopressin cells.Brain Res 1993; 613:164–167.

    Article  CAS  PubMed  Google Scholar 

  37. Day T, Randle J, Renaud L. Opposing α and β-adrenergic mechanisms mediate dose dependant actions of noradrenaline on supraoptic neuronesin vivo.Brain Res 1985; 358:171–9.

    Article  CAS  PubMed  Google Scholar 

  38. Lightman S, Todd K, Everitt B. Ascending noradrenergic projections from the brainstem: evidence for a major role in the regulation of blood pressure and vasopressin secretion.Exp Brain Res 1984; 55:145–151.

    Article  CAS  PubMed  Google Scholar 

  39. Heal D, Butler S, Prow M, Buckett R. Quantification of presynapticα 2-adrenoceptors in rat brain after short term DSP-4 lesioning.Eur J Pharm 1993; 249:37–41.

    Article  CAS  Google Scholar 

  40. Black I, Petit C. Catecholamine enzymes in the degenerative neurological disease, idiopathic orthostatic hypotension.Sciences NY 1976; 192:910–12.

    Article  CAS  Google Scholar 

  41. Spokes E, Bannister R, Oppenheimer D. Multiple System Atrophy with autonomic failure. Clinical, histological and neurochemical observations in four cases.J Neural Sci 1979; 43:59–82.

    Article  CAS  Google Scholar 

  42. Tsai A, Maehara K, Iizuka R. Loss of catecholaminergic neurones in the hypothalamus of MSA.Rinsho Shinkeigaku. 1992; 32:125–130.

    CAS  PubMed  Google Scholar 

  43. Benarroch E, Smithson I, Low P, Parisi J. Depletion of catecholamine neurones of the rostral ventrolateral medulla in multiple system atrophy with autonomic failure.Ann Neurol 1998; 43:156–163.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. Kimber M.R.C.P..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kimber, J., Watson, L. & Mathias, C.J. Abnormal suppression of arginine-vasopressin by clonidine in multiple system atrophy. Clinical Autonomic Research 9, 271–274 (1999). https://doi.org/10.1007/BF02319457

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02319457

Keywords

Navigation