title: Glucocorticoids regulate Na+ transport in vascular smooth muscle through the glucocorticoid receptor-mediated mechanism.
abstract: The incidence of hypertension in conditions of chronic glucocorticoid (GC) excess is very high, though the mechanism whereby GC elevate blood pressure is far from being understood. We have recently found that GC markedly increase influx of Na+ in vascular smooth muscle (VSM) cells. We and other investigators have previously described receptors for GC in arterial tissues, and we have now examined whether the effect of GC on Na+ transport in VSM is mediated through these receptors. Vascular smooth muscle cells were cultured from rabbit aortas. The cells were treated for 48 h with 10(-7) mol/L dexamethasone (DEX), in the presence or absence of RU 486, a competitive inhibitor of DEX binding to its receptor, or progesterone, an allosteric accelerator of DEX dissociation from the receptor. Unidirectional influx of Na+ was measured with 22Na as tracer. Dexamethasone more than doubled the influx rate of Na+, RU 486 completely prevented this increase, and progesterone reduced the DEX-induced increase by approximately 80%. The time of the cell exposure to DEX necessary for the DEX effect to occur was 4 to 6 h, with a maximal effect at 48 h, suggesting a genomic effect. Addition of protein synthesis inhibitors, actinomycin D or cycloheximide, to VSM cells cultured in the presence of DEX prevented the increase of Na+ influx by DEX.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Rush Medical College, Chicago, Illinois.
authors.forename: L
authors.initials: L
authors.lastname: Kornel
authors.forename: B
authors.initials: B
authors.lastname: Manisundaram
authors.forename: W A
authors.initials: WA
authors.lastname: Nelson
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011817:Rabbits; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes
chemical_list: D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D011965:Receptors, Glucocorticoid; D012979:Sodium Radioisotopes; D015735:Mifepristone; D003907:Dexamethasone; D012964:Sodium