Mineralocorticoid-induced increase in β-adrenergic receptors of cultured rat arterial smooth muscle cells

Abstract

We have investigated the effect of mineralocorticoids on β-adrenergic receptors in cultured arterial smooth muscle cells. Mineralocorticoid (aldosterone) treatment resulted in a significant increase in β-adrenergic receptors measured by [ 3H]dihydroalprenolol (DHA) binding. This effect required at least 20 hours of incubation with aldosterone and was completely blocked by cycloheximide (10 μg/ml), indicating protein synthesis was required for this response. Aldosterone at the concentration range of 10 −8–10 −6M increased [ 3H]DHA binding, but was ineffective at 10 −9 M. Scatchard analysis of [ 3H]DHA binding revealed that the observed significant increase in binding was due to an increased number of binding sites ( P < 0.05), and that the affinity was unchanged. The aldosterone (1 × 10 −8 M) effect was completely blocked by the combination of RU 38486 (10 −6M) and spironolactone (10 −7 M), but not by the glucocorticoid antagonist RU 38486 alone. While basal c-AMP levels were not changed by aldosterone (10 −6 M) treatment, the isoproterenol (10 −6 M) stimulated level of c-AMP was significantly higher in cells treated with aldosterone ( P < 0.05). We conclude that aldosterone, acting through the mineralocorticoid receptor, has a direct effect on arterial smooth muscle cells mediated through modulation of β-adrenergic receptors of these cells.