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
beta-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 beta 2-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 beta-
adrenoceptor abnormality in the first patient: however, in the second patient, there were no measurable beta-
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 thrombocyte 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 beta-
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 beta-
adrenergic sensitization leading to blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)