EFFECT OF VLDL ON THE INHIBITION OF ARACHIDONIC-ACID TRANSFORMATION BY DEXAMETHASONE IN CULTURED SMOOTH-MUSCLE CELLS

Very-low-density lipoproteins (VLDL) induce a dose-dependent reduction (up to 55%) in the number of specific binding sites and about a 2-fold increase in binding affinity for [H-3]dexamethasone in human and rat smooth muscle cells (SMC). Maximal effect of VLDL was achieved within 3-5 h at a lipoprotein concentration 60 mug protein/ml. Lipoprotein-mediated reduction in the number of [H-3]dexamethasone binding sites resulted in partial loss of cellular sensitivity to hormone action: dexamethasone (1 . 10(-6)M) inhibited the transformation of [C-14]arachidonic acid (AA) into metabolites to a lesser extent in SMC preincubated with VLDL (11.5%) than in untreated cells (29.0%). In particular, under these conditions the inhibitory effect of dexamethasone on prostaglandin I2 (PGI2) formation in VLDL-treated SMC was lower than in untreated cells (42.1% vs. 60%). We propose that VLDL is able to counteract the inhibitory effect of glucocorticoids on AA release and PGI2 formation in vascular SMC by reduction of cellular specific glucocorticoid binding sites.