GLUCOCORTICOIDS BUT NOT MINERALOCORTICOIDS MODULATE ENDOTHELIN-1 AND ANGIOTENSIN-II BINDING IN SHR VASCULAR SMOOTH-MUSCLE CELLS

Both glucocorticoids and mineralocorticoids are involved in circulator y homeostasis and blood pressure control. In recent years direct effec ts of both steroid classes on vascular smooth muscle cells (VSMC) have been reported. We have thus examined the effects of RU 28362, a pure glucocorticoid agonist, and aldosterone, the physiologic mineralocorti coid, on the binding to VSMC from spontaneously hypertensive rats (SHR ) of two key vasoactive peptides, endothelin-1 and angiotensin II. Bin ding of angiotensin II rose, and that of endothelin-1 declined, in a t ime- and dose-dependent fashion with maximal effects observed at 24 h and half-maximal effects for each at 2-3 nM RU 28362. Scatchard analys is showed that for both endothelin-1 and angiotensin II, RU 28362 alte rs receptor number but not affinity; competition studies with receptor -selective ligands (BQ123, S6C, DuP753 and PD123319) show that glucoco rticoids specifically elevate (X2) AT-1 receptors and specifically low er (to similar to 30%) levels of ET(A) receptors. Treatment of VSMC wi th the antiglucocorticoid RU 38486 reversed the effect of glucocortico ids on endothelin-1 and angiotensin II binding, confirming the Type II (glucocorticoid) receptor mediated effect of the glucocorticoids. Ald osterone (100 nM) also lowers endothelin-1 binding and increases angio tensin II binding in VSMC; that this effect reflects aldosterone occup ancy of classical glucocorticoid receptors is shown by the blockade of the aldosterone effect by an equal concentration (100 nM) of RU 38486 -i.e. there is no evidence for an action of aldosterone via mineraloco rticoid receptors. We interpret our results as evidence for a complex modulation of receptors for vasoactive peptides in VSMC by glucocortic oid but not mineralocorticoid hormones.