Glucocorticoids but not mineralocorticoids modulate endothelin-1 and angiotensin II binding in SHR vascular smooth muscle cells

J Steroid Biochem Mol Biol. 1995 Mar;52(3):219-25. doi: 10.1016/0960-0760(94)00168-l.

Abstract

Both glucocorticoids and mineralocorticoids are involved in circulatory homoeostasis and blood pressure control. In recent years direct effects 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 mineralocorticoid, on the binding to VSMC from spontaneously hypertensive rats (SHR) of two key vasoactive peptides, endothelin-1 and angiotensin II. Binding of angiotensin II rose, and that of endothelin-1 declined, in a time- and dose-dependent fashion with maximal effects observed at 24 h and half-maximal effects for each at 2-3 nM RU 28362. Scatchard analysis showed that for both endothelin-1 and angiotensin II, RU 28362 alters receptor number but not affinity; competition studies with receptor-selective ligands (BQ123, S6C, DuP753 and PD123319) show that glucocorticoids specifically elevate (X2) AT-1 receptors and specifically lower (to approximately 30%) levels of ETA receptors. Treatment of VSMC with the antiglucocorticoid RU 38486 reversed the effect of glucocorticoids on endothelin-1 and angiotensin II binding, confirming the Type II (glucocorticoid) receptor mediated effect of the glucocorticoids. Aldosterone (100 nM) also lowers endothelin-1 binding and increases angiotensin II binding in VSMC; that this effect reflects aldosterone occupancy 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 mineralocorticoid receptors. We interpret our results as evidence for a complex modulation of receptors for vasoactive peptides in VSMC by glucocorticoid but not mineralocorticoid hormones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / pharmacology
  • Androstanols / pharmacology*
  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists
  • Animals
  • Biphenyl Compounds / pharmacology
  • Cells, Cultured
  • Endothelin Receptor Antagonists
  • Endothelins / metabolism*
  • Glucocorticoids / agonists
  • Glucocorticoids / pharmacology*
  • Hypertension / metabolism*
  • Imidazoles / pharmacology
  • Losartan
  • Male
  • Mifepristone / pharmacology
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Peptides, Cyclic / pharmacology
  • Rats
  • Rats, Inbred SHR
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin / agonists
  • Receptors, Glucocorticoid / agonists
  • Receptors, Mineralocorticoid / agonists
  • Tetrazoles / pharmacology
  • Viper Venoms / pharmacology

Substances

  • Androstanols
  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Endothelin Receptor Antagonists
  • Endothelins
  • Glucocorticoids
  • Imidazoles
  • Peptides, Cyclic
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Tetrazoles
  • Viper Venoms
  • sarafotoxins s6
  • Angiotensin II
  • Mifepristone
  • Aldosterone
  • 11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one
  • Losartan
  • cyclo(Trp-Asp-Pro-Val-Leu)