Klinische Wochenschrift

, Volume 67, Issue 19, pp 1004–1009 | Cite as

Beta-adrenergic blood pressure regulation in shy-drager syndrome and pheochromocytoma

  • M. Middeke
  • J. Ittner
  • M. Mezger
  • S. Reder
  • J. Remien


Both Shy-Drager syndrome and pheochromocytoma are characterized by an abnormal catecholamine secretion, e.g. a reduced secretion in Shy-Drager syndrome, and an excessive stimulation in pheochromocytoma resulting in adrenergic dysfunction and in adrenergic hyperactivity, respectively. The relationship between extreme variations in circulating catecholamines and β-adrenergic receptor activity was studied in two patients with severe orthostatic hypotension (Shy-Drager syndrome) and in a patient with pheochromocytoma with excessive spontaneous catecholamine increases using the lymphocyte β2-adrenoceptor assay. In both patients with Shy-Drager syndrome, basal plasma concentrations of epinephrine and dopamine were low under resting conditions and could not be stimulated in the upright position. Norepinephrine was low in the first patient, and could not be stimulated; whereas the second patient had a normal basal concentration of norepinephrine, which could be moderately stimulated. There was no β-adrenoceptor abnormality in the first patient; however, in the second patient, there were no measurable β-adrenoceptors on membrane fractions, whereas a population of receptors only in the low affinity state could be identified on intact cells. Alpha-adrenoceptor density on thromboycte membranes was slightly increased in both patients with Shy-Drager syndrome and showed no substantial change during upright posture. Catecholamine increases in the pheochromocytoma patient were accompanied by a rise in blood pressure, bradycardia, and an acute up-regulation of β-adrenoceptors. Plasma concentrations of cAMP paralleled the increase in receptor density and blood pressure. The findings in pheochromocytoma add support to the theory that an acute catecholamine stimulation gives rise to an acute β-adrenergic sensitization leading to blood pressure elevation.

In Shy-Drager syndome, we found no β-adrenoceptor up-regulation in the orthostatic position (first patient) since catecholamines were not stimulated. Although there was an acute up-regulation due to a moderate norepinephrine stimulation (second patient) during posture orthostatic hypotension could not be prevented. Alpha-adrenoceptor expression was normal in both patients. Thus, in orthostatic hypotension the function of the β2-adrenoceptor system seems to be disturbed since either norepinephrine is not secreted in sufficient amounts to induce β2-receptor up-regulation or the β2-receptor is in a low affinity (uncoupled) state. From these observations in Shy-Drager syndrome and in pheochromocytoma, it is concluded that adrenergic blood pressure regulation is dependent on a normal catecholamine secretion, alpha-adrenoceptor function, and a normal β-adrenoceptor population, as well as affinity with an intact β-adrenergic regulation.

Key words

Shy-Drager syndrome Pheochromocytoma Adrenoceptors cAMP  Catecholamines 



Mean arterial blood pressure


Heart rate


Maximal binding sites


Dissociation constant


Cyclic adenosine-monophosphate






Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Anhäupl T, Liebl B, Remien J (1988) Kinetic and equilibrium studies of (—)125Iodocyanopindolol binding to β-adrenoceptors on human lymphocytes: evidence for the existence of two classes of binding sites. J Recep Res 8(1–4):47–57Google Scholar
  2. 2.
    Borkowski KR, Quinn P (1984) β2-adrenoceptors mediate adrenaline's facilitation of neurogenic vasoconstriction. Eur J Pharmacol 103:339–342Google Scholar
  3. 3.
    Bristow MR, Ginsburg R, Minobe W et al. (1982) Decreased catecholamine sensitivity and β-adrenergic receptor density in failing human heart. N Engl J Med 307:205–211Google Scholar
  4. 4.
    Brodde O-E, Prywarra A, Daul A, Anlauf M, Bock KD (1984) Correlation between lymphocyte β2-adrenoceptor density and mean arterial blood pressure: elevated β-adrenoceptors in essential hypertension. J Cardiovasc Pharmacol 6:678–682Google Scholar
  5. 5.
    Brodde O-E, Beckeringh JJ, Michel MC (1987) Human heart β-adrenoceptors: a fair comparison with lymphocyte β-adrenoceptors? Trends Pharmacol Sci 8:403–407Google Scholar
  6. 6.
    Brodde O-E, Michel MC, Nohlen M, Wang XL, Zerkowski H-R (1988) The relevance of determination of lymphocyte β2-adrenoceptors as index for β-adrenoceptors in other human tissues. Br J Pharmacol 93 (Suppl):27 (Abstract)Google Scholar
  7. 7.
    Bruschi G, Orlandini G, Pavarani C, Spaggiari M, Tacinelli L, Cavatorta A (1984) Lymphocytic beta-adrenoceptor abnormality in primary hypertension. IRCS Med Sci (Biochem) 12:461–462Google Scholar
  8. 8.
    Chobanian AV, Tifft CP, Sackel H, Pitruzella A (1982) Alpha and beta adrenergic receptor activity in circulating blood cells of patients with idiopathic orthostatic hypotension and pheochromocytoma. Clin Exp Hypertens A4:793–806Google Scholar
  9. 9.
    Daiguji M, Meltzer HY, Prichard DCU (1981) Human platelet alpha2-adrenergic receptors: labeling with 3H-yohimbine, a selective antagonist ligand. Life Sci 28:2705–2717Google Scholar
  10. 10.
    Hui KKP, Conolly ME (1981) Increased numbers of beta receptors in orthostatic hypotension due to autonomic dysfunction. N Engl J Med 304:1473–1476Google Scholar
  11. 11.
    Liebl B, Anhäupl Th, Haen E, Remien J (1988) Effect of thiols on β2-adrenoceptors in human mononuclear leucocytes. Naunyn-Schmiedberg's Arch Pharmacol 338:523–528Google Scholar
  12. 12.
    Liebl B, Remien J (1989) Competition of β-adrenoceptor agonists with high and low affinity binding sites for125Iodocyanopindolol in human mononuclear leucocytes. Naunyn-Schmiedeberg's Arch Pharmacol 339 (Suppl), Abstract 367Google Scholar
  13. 13.
    Majewski H (1983) Modulation of noradrenaline release through activation of presynaptic β-adrenoceptors. J Autonom Pharmacol 3:47Google Scholar
  14. 14.
    Middeke M, Remien J, Block LH, Kirzinger S, Landrock A, Holzgreve H (1983) Beta2-adrenoceptor density on membranes and on intact mononuclear cells in essential hypertension. Res Exp Med 183:227–232Google Scholar
  15. 15.
    Middeke M, Remien J, Holzgreve H (1984) The influence of sex, age, blood pressure and physical stress on β2-adrenoceptor density on mononuclear cells. J Hypertens 2:261–264Google Scholar
  16. 16.
    Middeke M, Kirzinger S, Remien J, Krahl B, Holzgreve H (1986) An altered acute regulation of the β-adrenoceptoradenylate cyclase system in patients with essential hypertension at rest and under exercise. Clin Exp Hypertens (Abstr) A8:135–136Google Scholar
  17. 17.
    Middeke M, Lohmöller G, Remien J et al. (1988) Acute regulation of lymphocyte β-adrenoceptor activity in pheochromocytoma. Klin Wochenschr 66:187–189Google Scholar
  18. 18.
    Pfeifer MA, Ward K, Malpass T et al. (1984) Variations in circulating catecholamines fail to alter human platelet alpha-2-adrenergic receptor number or affinity for [3H]yohimbine or [3H]dihydroergocryptine. J Clin Invest 74:1063–1072Google Scholar
  19. 19.
    Remien J (1984) β-adrenoceptor recognition sites in living lymphocytes: a model for receptor properties in human disease? Eur J Respir Dis 65 (Suppl 135):208–214Google Scholar
  20. 20.
    Shy GM, Drager GA (1960) A neurological syndrome associated with orthostatic hypotension: a clinical-pathologic study. Arch Neurol 2:511–527Google Scholar
  21. 21.
    Tohmeh JF, Cryer PE (1980) Biphasic adrenergic modulation of β-adenergic receptors in man. J Clin Invest 65:836–840Google Scholar
  22. 22.
    Ziegler MG, Lake CR, Kopin IJ (1977) The sympathetic nervous system defect in primary orthostatic hypotension. N Eng J Med 296:293Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • M. Middeke
    • 1
  • J. Ittner
    • 3
  • M. Mezger
    • 3
  • S. Reder
    • 1
  • J. Remien
    • 2
  1. 1.Medizinische PoliklinikGermany
  2. 2.Walther-Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians-Universität MünchenGermany
  3. 3.I. Medizinische Klinik der Universität UlmGermany

Personalised recommendations