Key Points
- To determine how glucocorticoid exposure modulates angiotensin II type 1 receptor density, gene expression, and downstream postreceptor signaling in vascular smooth muscle cells.
- Treated vascular smooth muscle cells with 1 mumol/L dexamethasone with or without the glucocorticoid antagonist RU 38486 to assess receptor density (Bmax) and binding affinity.
- Evaluated postreceptor mechanisms by measuring GTP analogue-induced inositol trisphosphate production and Gq alpha protein levels in permeabilized cells.
- Measured steady-state messenger RNA levels of the angiotensin II type 1 receptor at 30 minutes and 24 hours after dexamethasone exposure.
- Dexamethasone increased receptor density from 15 +/- 3 fmol/mg protein in control cells to 27 +/- 3 fmol/mg protein at 48 hours without altering binding affinity, an effect fully blocked by RU 38486.
- Angiotensin II type 1 receptor mRNA increased 2.2 +/- 0.3-fold after 30 minutes and 7.8 +/- 0.4-fold after 24 hours of dexamethasone treatment.
- Dexamethasone pretreatment had no significant effect on GTP analogue-stimulated inositol trisphosphate production or Gq alpha protein levels.
Structured PICO
PPopulationVascular smooth muscle cells
IInterventionDexamethasone (1 mumol/L) for up to 48 hours
CComparatorControl cells (untreated) and cells treated with glucocorticoid antagonist RU 38486
OOutcomeAngiotensin II type 1 receptor number (Bmax) and messenger RNA levelssurrogate
Dexamethasone increases angiotensin II type 1 receptor gene expression and receptor density in vascular smooth muscle cells via glucocorticoid-specific receptors.