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 hypertension. We examined the effects of glucocorticoids on V-1a arginine vasopressin receptor mRNA and protein levels in vascular smooth muscle cells. Dexamethasone (1 mu mol/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.