Mechanism of the effects of glucocorticoids and mineralocorticoids on vascular smooth muscle contractility.
We have previously demonstrated that receptors to both mineralocorticoids (MC) and glucocorticoids (GC) exist in the arterial wall and that treatment with GC markedly increases Na+ and Ca2+ influx in cultured aortic vascular smooth muscle (VSM) cells, whereas treatment with MC increases only Na+ influx. We now report the results of the study aimed at the elucidation of the mechanism(s) of these effects. Unidirectional influx of Na+ and Ca2+ was measured in cultured cells of rabbit aortic media, using 22Na and 45Ca as tracers, in the presence of ouabain. The cells were treated for different periods with dexamethasone (DEX) or aldosterone (ALDO) in physiologic or supraphysiologic concentrations, in the presence or absence of competitive inhibitors of GC-receptor binding, RU 486, or MC-receptor binding, K-prorenoate. DEX in 50 nM concentration increased Na+ influx by 98 +/- 18% and Ca2+ influx by 100 +/- 20%, and the maximum effect was seen after 48 hour cell-treatment. ALDO in 5 nM concentration increased Na+ influx by 90 +/- 12% and had no effect on Ca2+ influx, and the maximum effect was seen after 7-10 days of cell-treatment. The enhancing effect of both DEX and ALDO on the influx rate of Na+ was prevented by actinomycin D and by cycloheximide. RU 486 completely inhibited DEX from exercising its enhancing effect on Na+ influx, but diminished influx rate of Na+ increased by ALDO only by 25%. Prorenoate (PRN) did not have any effect on DEX-increased Na+ influx, but completely inhibited ALDO from exercising its effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Kornel
L
L
Department of Medicine, Rush-Presbyterian-St. Luke's Medical Center Chicago, IL 60612.
Nelson
W A
WA
Manisundaram
B
B
Chigurupati
R
R
Hayashi
T
T
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000494:pharmacology*; D008901:Mineralocorticoids / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism
D005938:Glucocorticoids; D008901:Mineralocorticoids; D012964:Sodium; D002118:Calcium