Glucocorticoid treatment reduces prostacyclin synthesis in response to limited stimuli

Abstract

Dexamethasone 21-acetate (DMS 21-A) time-and dose-dependently suppressed bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells. The suppression was more prominent in the presence of pertussis toxin, which by itself could enhance bradykinin-induced prostacyclin synthesis. The DMS 21-A treatment diminished prostacyclin synthesis also in response to vasopressin. In contrast, it did not affect prostacyclin synthesis in response to arachidonic acid or A23187. Melittin-induced prostacyclin synthesis was reduced only at low doses (1–7 x 10 −7M). The suppression of bradykinin-induced prostacyclin synthesis by DMS 21-A was completely blocked by cycloheximide. DMS 21-A had no effect on the cellular level of lipocortin I protein, but increased the antiphospholipase A 2 activity in EDTA extracts of the cells. These results suggest that the DMS 21-A treatment induces phospholipase A 2 inhibitor protein(s) other than lippcortin I and reduces prostacyclin production in response to limited stimuli.