(Hypertension. 1997;30:1274-1278.)
© 1997 American Heart Association, Inc.
Articles |
Impaired Cortisol Binding to Glucocorticoid Receptors in Hypertensive Patients
From the Department of Medicine and Experimental Oncology, University of Turin, Italy (P.M., D.S., A.R., G.M., L.C., F.V.), and the Departments of Clinical Biochemistry (M.P.) and Medicine (C.J.K.), University of Edinburgh, UK.
Correspondence to Paolo Mulatero, MD, Cattedra Medicina Interna, Ospedale San Vito, Strada San Vito 34, 10133 Torino, Italy.
Abstract We compared glucocorticoid receptor binding characteristics and glucocorticoid responsiveness of human mononuclear leukocytes (HML) from hypertensive patients and matched normotensive volunteers. We also considered associations of these variables with plasma renin activity, aldosterone, cortisol, corticotropin, and electrolyte concentrations. We calculated binding affinity (Kd; nmol/L) and capacity (Bmax; sites/cell) for dexamethasone and cortisol from homologous and heterologous competition curves for specific [3H]dexamethasone binding sites on HML isolated from the blood of normotensive volunteers and subjects with essential hypertension. Glucocorticoid responsiveness of HML was evaluated as IC50 values (nmol/L) for dexamethasone and cortisol for the inhibition of lysozyme release. We measured plasma hormones by radioimmunoassay. Kd values (mean±SE) for cortisol in HML of hypertensive patients were higher than in control subjects (24.6±2.4 versus 17.5±1.7 nmol/L, P<.04). Binding capacity (4978±391 versus 4131±321 sites/cell), Kd values for dexamethasone (6.7±0.5 versus 5.7±0.3 nmol/L), and IC50 values for dexamethasone (3.4±0.3 versus 3.1±0.2 nmol/L) and cortisol (12.2±1.6 versus 9.5±0.3 nmol/L) were not significantly different. Patients with renin values less than 0.13 ng angiotensin I/L per second were markedly less sensitive to cortisol than those with higher values. Both Kd (30.3±2.5 versus 19.2±2.4 nmol/L) and IC50 values (15.5±1.8 versus 8.9±1.2 nmol/L) for cortisol were significantly higher in patients with lower renin values (P<.03). Other variables, including plasma hormone and electrolyte values and binding characteristics for dexamethasone, were not different. These data suggest that cortisol binding to glucocorticoid receptor is slightly impaired in patients with essential hypertension. In vivo, this could lead to inappropriate binding of cortisol to mineralocorticoid receptors. Hence, decreased sensitivity to cortisol is associated with renin suppression. This hypothesis is supported by evidence of hypertension and low renin activity, which others have described in patients with primary glucocorticoid resistance due to mutations of the glucocorticoid receptor.
Key Words: glucocorticoid receptors • hypertension • cortisol
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