EFFECTS OF BRIEF GLUCOCORTICOID EXPOSURE ON GROWTH OF VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE

While prolonged exposure of vascular smooth muscle cells (VSMC) to glu cocorticoid has been shown to inhibit cell proliferation, the effect o f a brief pulse exposure is not known. We studied the short-term effec ts of pulse exposure to dexamethasone (DEX) on DNA synthesis in cultur ed VSMC, VSMC were pulsed with DEX for varying time intervals and [H-3 ]thymidine incorporation into cells after 24 h was measured. Exposure to DEX for 24 h decreased [H-3]thymidine incorporation, while pulse tr eatments with DEX from 2 min to 6 h significantly increased [H-3]thymi dine incorporation. Maximal proliferative effect was observed with a 2 0-min exposure. The effect of a 20-min pulse was dose-dependent, with the half-maximal dose of DEX being approximately 10(-7) M. A selective glucocorticoid re ceptor antagonist, RU486, inhibited the proliferati ve effect of DEX, Concentrated conditioned medium from cells exposed t o 10(-6) M DEX increased [H-3]thymidine incorporation by other VSMC in a dose-dependent manner. These results suggest that short term pulse DEX exposure is capable of producing one or more autocrine growth fact ors in VSMC via a glucocorticoid receptor action. This effect of gluco corticoid pulses may contribute to the pathogenesis of arteriosclerosi s and hypertension. (C) 1998 Academic Press.