Glucocorticoid modulation of β-adrenergic receptors of cultured rat arterial smooth muscle cells

Since both glucocorticoids and catecholamines are involved in the regulation of normal blood pressure, we investigated the modulation of β-adrenergic receptors of cultured rat arterial smooth muscle cells by glucocorticoids. The synthetic glucocorticoids dexamethasone and RU 28362, at 10^-8 M concentration, increased maximum β-adrenergic binding but had no effect on the dissociation constant (K(d)). Each steroid caused an increase in maximum [³H]dihydroalprenonol binding over the concentration range of 10^-8 to 10^-6 M, but not at 10^-9 M. The glucocorticoid effect on β-adrenergic receptors of arterial smooth muscle cells required a minimum of 20 hours of incubation in the presence of the steroid and was significantly inhibited by cycloheximide (10 μg/ml), indicating that the glucocorticoid effect required protein synthesis. The effect of dexamethasone on [³H]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 glucocorticoid-induced increase in β-adrenergic receptor binding. While causing no change in the basal cAMP level, treatment of arterial smooth muscle cells with 10^-6 M dexamethasone for 24 hours increased the 10^-6 M isoproterenol-stimulated cAMP levels.