GLUCOCORTICOIDS REGULATE V-1A VASOPRESSIN RECEPTOR EXPRESSION BY INCREASING MESSENGER-RNA STABILITY IN VASCULAR SMOOTH-MUSCLE CELLS

Enhancement of vascular responsiveness is considered to be one of the major contributing factors observed in glucocorticoid-induced hyperten sion. We examined the effects of glucocorticoids on V-1a arginine vaso pressin receptor mRNA and protein levels in vascular smooth muscle cel ls. Dexamethasone (1 mu mol/L) produced a 1.8-fold increase in V-1a re ceptor density without changing its affinity. Steady-state values of V -1a receptor mRNA, analyzed by Northern blotting, increased 2.7-fold a fter a 12-hour exposure to dexamethasone. This effect of dexamethasone was blocked by the glucocorticoid antagonist RU38486 and did not occu r in the presence of the protein synthesis inhibitor cycloheximide. Th e V-1a receptor gene transcription rate, determined by nuclear run-off assays, was unchanged in cells treated with dexamethasone for 12 hour s. Dexamethasone increased the half-life of V-1a receptor mRNA by 2.2- fold. These findings suggest that dexamethasone upregulates the expres sion of the V-1a receptor by increasing mRNA stability rather than by gene transcription and that de novo protein synthesis is involved in t his regulation.