Glucocorticoids but not mineralocorticoids modulate endothelin-1 and angiotensin II binding in SHR vascular smooth muscle cells. 1995

P H Provencher, and J Saltis, and J W Funder
Baker Medical Research Institute, Victoria, Australia.

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.

UI MeSH Term Description Entries
D006973 Hypertension Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more. Blood Pressure, High,Blood Pressures, High,High Blood Pressure,High Blood Pressures
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008297 Male Males
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010456 Peptides, Cyclic Peptides whose amino acid residues are linked together forming a circular chain. Some of them are ANTI-INFECTIVE AGENTS; some are biosynthesized non-ribosomally (PEPTIDE BIOSYNTHESIS, NON-RIBOSOMAL). Circular Peptide,Cyclic Peptide,Cyclic Peptides,Cyclopeptide,Orbitide,Circular Peptides,Cyclopeptides,Orbitides,Peptide, Circular,Peptide, Cyclic,Peptides, Circular
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D011965 Receptors, Glucocorticoid Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example. Corticoid Type II Receptor,Glucocorticoid Receptors,Glucocorticoids Receptor,Corticoid II Receptor,Corticoid Type II Receptors,Glucocorticoid Receptor,Receptors, Corticoid II,Receptors, Corticoid Type II,Receptors, Glucocorticoids,Corticoid II Receptors,Glucocorticoids Receptors,Receptor, Corticoid II,Receptor, Glucocorticoid,Receptor, Glucocorticoids
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005938 Glucocorticoids A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. Glucocorticoid,Glucocorticoid Effect,Glucorticoid Effects,Effect, Glucocorticoid,Effects, Glucorticoid
D000450 Aldosterone A hormone secreted by the ADRENAL CORTEX that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Aldosterone, (+-)-Isomer,Aldosterone, (11 beta,17 alpha)-Isomer

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