ISSN:
1432-1440
Keywords:
Shy-Drager syndrome
;
Pheochromocytoma
;
Adrenoceptors
;
cAMP
;
Catecholamines
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01716065
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