Glucocorticoid Modulation of j3-Adrenergic Receptors of Cultured Rat Arterial Smooth Muscle Cells

Since both ghicocortkoids and catecholamines are involved in the regulation of normal blood pressure, we Investigated the modulation of /3-adrenergic receptors of cultured rat arterial smooth muscle cells by glucocorticoids. The synthetic glucocorticoids dexamethasone and RU 28362, at 10~ M concentration, increased maximum 0-adrenergic binding but had no effect on the dissociation constant (£d). Each steroid caused an Increase hi maTimnm [^dihydroalprenolol binding over the concentration range of 10~ to 10"* M, but not at 10~ M. The glucocorticoid effect on /3-adrenergk receptors of arterial smooth muscle cells required a minlmnm of 20 hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximlde (10 Mg/ml), indicating that the glucocorticoid effect required protein synthesis. The effect of dexamethasone on [H]dihydroalprenolol binding was significantly inhibited by the glucocorticoid antagonist RU 38486. Basal and agonist-stimulated cyclic adenosine 3',5'-monophosphate (cAMP) levels In arterial smooth muscle cells, before and after glucocorticoid treatment, were measured as an indicator of the physiological significance of the observed glucocorticoidinduced increase in 0-adrenergic receptor binding. While causing no change in the basal cAMP level, treatment of arterial smooth muscle cells with 10 ~* M dexamethasone for 24 hours increased the 10"* M isoproterenol-stimulated cAMP levels. (Hypertension 12: 393-398, 1988)