GLUCOCORTICOID INHIBITS CAMP PRODUCTION INDUCED BY VASOACTIVE AGENTS IN AORTIC SMOOTH-MUSCLE CELLS

It is well-known that atherosclerotic change and hypertension are comm on manifestations in patients with glucocorticoid excess. We previousl y reported that pituitary adenylate cyclase activating polypeptide (PA CAP), prostaglandin E(2) (PGE(2)) and carbacyclin, a stable analog of prostacyclin, have suppressive effects on vasopressin-induced DNA synt hesis of rat aortic smooth muscle cells through cAMP production (Muras e et al., J. Hypertens, 10 (1992) 1505; Oiso et al., Biochem. Cell, Bi ol., 71 (1993) 156). In the present study, we investigated the effect of glucocorticoid on cAMP production induced by PACAP, PGE(2) and carb acyclin in aortic smooth muscle cells. The pretreatment with dexametha sone significantly inhibited cAMP accumulation induced by these vasoac tive agents in a dose dependent manner in the range between 10 pM and 10 nM. These inhibitory effects of dexamethasone were dependent on the time of pretreatment up to 8 h. Dexamethasone inhibited cAMP accumula tion induced by NaF, a GTP-binding protein activator, and forskolin wh ich directly activates adenylate cyclase. Moreover, forskolin-induced adenylate cyclase activity was significantly reduced in membranes prep ared from the cells treated with dexamethasone. These results strongly suggest that glucocorticoid inhibits cAMP production induced by vasoa ctive agents in primary cultured rat aortic smooth muscle cells and th e inhibitory effect is exerted at the level of adenylate cyclase.