Glucocorticoids Regulate V 1a Vasopressin Receptor Expression by Increasing mRNA Stability in Vascular Smooth Muscle Cells

Abstract

Abstract Enhancement of vascular responsiveness is considered to be one of the major contributing factors observed in glucocorticoid-induced hypertension. We examined the effects of glucocorticoids on V 1a arginine vasopressin receptor mRNA and protein levels in vascular smooth muscle cells. Dexamethasone (1 μmol/L) produced a 1.8-fold increase in V 1a receptor density without changing its affinity. Steady-state values of V 1a receptor mRNA, analyzed by Northern blotting, increased 2.7-fold after a 12-hour exposure to dexamethasone. This effect of dexamethasone was blocked by the glucocorticoid antagonist RU38486 and did not occur in the presence of the protein synthesis inhibitor cycloheximide. The V 1a receptor gene transcription rate, determined by nuclear run-off assays, was unchanged in cells treated with dexamethasone for 12 hours. Dexamethasone increased the half-life of V 1a receptor mRNA by 2.2-fold. These findings suggest that dexamethasone upregulates the expression of the V 1a receptor by increasing mRNA stability rather than by gene transcription and that de novo protein synthesis is involved in this regulation.