Glucocorticoids increase preproendothelin-1 expression in rat aorta

Glucocorticoids play an important role in circulatory homeostasis. They mod ulate peripheral resistance by their direct action on blood vessels. We hav e previously shown that glucocorticoids increase preproendothelin-l gene tr anscription rate in vascular smooth muscle cells (Morin C et al. 1998, BBRC 244:583). Endothelin-l is a potent vasoactive peptide involved in the main tenance of vascular tone as well as in pathophysiological states. In this r eport we show that glucocorticoids increase preproendothelin-l expression i n rat aorta. The rise in preproendothelin-l steady state mRNA level is dose -dependent with a maximal 2.3-fold stimulation 8 hours following a 0.35 and a 2.5 mg/kg dexamethasone injection. A lower dose of dexamethasone (0.13 m g/kg) also increased preproendothelin-l expression in rat aorta. Since endo thelin-l levels are regulated at the transcriptional step, the increase in mRNA is likely to be paralleled by increased protein synthesis and vasocons trictor action. Moreover, systolic blood pressure was significantly elevate d in rats who received the 0.35 and 2.5 mg/kg doses of dexamethasone. Toget her, our results strongly suggest that the increase in preproendothelin-l e xpression by glucocorticoids contributes to the regulatory action of these corticosteroids on blood pressure in health and disease.