From the University of Edinburgh, Department of Medicine, Western General
Hospital (B.R.W., J.P.N., M.P., R.A., J.R.S., D.J.W.), and Ladywell Medical
Centre (H.V.E., D.W.H.), Edinburgh; the MRC Environmental Epidemiology Unit,
Southampton General Hospital, Southampton (D.I.W.P.); and the University of
Glasgow, Department of General Practice, Woodside Health Centre, Glasgow
(G.C.M.W.), UK.
Abstract
Abstract—The association between
hypertension and insulin resistance might be explained by increased
activity of the principal glucocorticoid, cortisol. Recent data show
that the intensity of dermal vasoconstriction after topical application
of glucocorticoids is increased in patients with essential
hypertension. In this report, we examine whether increased
glucocorticoid sensitivity or secretion is associated with insulin
resistance and is a cause or consequence of hypertension. We studied 32
men (aged 47 to 56 years) from a cross-sectional study and 105 men
(aged 23 to 33 years) in whom predisposition to high blood pressure has
been defined by their own blood pressure and the blood pressures of
their parents. In both populations, increased dermal glucocorticoid
sensitivity was associated with relative hypertension, insulin
resistance, and hyperglycemia. In young men with higher blood pressure
whose parents also had high blood pressure, enhanced glucocorticoid
sensitivity was accompanied by enhanced secretion of cortisol, enhanced
ligand-binding affinities for dexamethasone in leukocytes,
and impaired conversion of cortisol to inactive metabolites (cortisone
and 5ß-dihydrocortisol). Increased tissue sensitivity to cortisol,
amplified by enhanced secretion of cortisol, is a feature of the
familial predisposition to high blood pressure rather than a secondary
effect of high blood pressure. It may be mediated by an abnormal
glucocorticoid receptor, and it may contribute to the association
between hypertension and insulin resistance.
© 1998 American Heart Association, Inc.
Rapid Communication
Increased Glucocorticoid Activity in Men With Cardiovascular Risk Factors
Key Words: receptors, corticosteroid • adrenal cortex hormones • blood pressure • insulin • blood vessels
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