Glucocorticoids increase preproendothelin-1 expression in rat aorta.

Glucocorticoids play an important role in circulatory homeostasis. They modulate peripheral resistance by their direct action on blood vessels. We have previously shown that glucocorticoids increase preproendothelin-1 gene transcription rate in vascular smooth muscle cells (Morin C et al. 1998, BBRC 244:583). Endothelin-1 is a potent vasoactive peptide involved in the maintenance of vascular tone as well as in pathophysiological states. In this report we show that glucocorticoids increase preproendothelin-1 expression in rat aorta. The rise in preproendothelin-1 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 mg/kg) also increased preproendothelin-1 expression in rat aorta. Since endothelin-1 levels are regulated at the transcriptional step, the increase in mRNA is likely to be paralleled by increased protein synthesis and vasoconstrictor action. Moreover, systolic blood pressure was significantly elevated in rats who received the 0.35 and 2.5 mg/kg doses of dexamethasone. Together, our results strongly suggest that the increase in preproendothelin-1 expression by glucocorticoids contributes to the regulatory action of these corticosteroids on blood pressure in health and disease.