(Hypertension. 1996;27:190-196.)
© 1996 American Heart Association, Inc.
Articles |
Increased Vasoconstrictor Sensitivity to Glucocorticoids in Essential Hypertension
From the Department of Medicine, Western General Hospital, University of Edinburgh (Scotland, UK), and the Research Institute, Children's Hospital, Oakland, Calif (C.H.L.S.).
Abstract Glucocorticoids raise blood pressure but were
thought not to play a pathophysiological role
in essential hypertension when it was demonstrated that cortisol
secretion rates and circulating concentrations are normal in this
disease. However, recent observations suggest that increased tissue
sensitivity to cortisol, mediated by either abnormal glucocorticoid
receptors or impaired inactivation of cortisol by
11ß-dehydrogenase, may allow cortisol to raise blood pressure
despite normal circulating concentrations. We studied 11 patients with
essential hypertension and 11 matched normotensive control subjects.
Dermal vasoconstriction after topical application of both cortisol
(16±4 versus 32±5 U, control subjects versus hypertensive
patients;
P<.02) and beclomethasone dipropionate (75±10 versus
100±7 U; P<.05) was increased in the hypertensive
patients. Hypothalamic-pituitary glucocorticoid receptor
sensitivity was normal, as judged by basal cortisol secretion rates and
suppression of plasma cortisol during sequential overnight
dexamethasone suppression tests. 11ß-Dehydrogenase
activity was impaired in essential hypertension, as judged by prolonged
half-lives of [11
-3H]cortisol (44±4 versus
58±4
minutes, control subjects versus hypertensive patients;
P<.02). However, this did not correlate with the dermal
vasoconstrictor response. We conclude that vasoconstrictor sensitivity
to glucocorticoids is increased in essential hypertension and that this
may initiate and/or sustain the increased peripheral
vascular resistance that characterizes this disease. The mechanism of
increased sensitivity remains uncertain, but it will be important to
establish whether it relates to genetic abnormalities of the
glucocorticoid receptor that have been observed in animal models and
young individuals who are predisposed to essential hypertension.
Key Words: glucocorticoids • hypertension, essential • skin • vasoconstriction • receptors, glucocorticoid • metabolism
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