DIFFERENTIAL REGULATION OF NA-K+-ATPASE GENE-EXPRESSION BY CORTICOSTEROIDS IN VASCULAR SMOOTH-MUSCLE CELLS()

To determine whether gluco- and mineralocorticoids have specific actio ns on Na+-K+-ATPase gene expression in vascular tissue, we used Northe rn blot analysis to compare the effects of dexamethasone (Dex) and ald osterone (Aldo) on Na+-K+-ATPase alpha(1)- and beta(1)-subunit mRNA ex pression in cultured vascular smooth muscle cells from rat aortae. Dex at 10(-6) M increased alpha(1)-mRNA level 2.5-fold at 24 h and beta(1 )-mRNA level 9.9-fold at 12 h. Aldo at 10(-6) M increased alpha(1)-mRN A level 2.7-fold at 48 h and beta(1)-mRNA level 10.9-fold at 6 h. The half-maximal stimulation of both alpha(1)- and beta 1-mRNA levels occu rred at a concentration of 5-7 x 10(-9) M Dex, whereas it occurred at a concentration of 2-3 x 10(-9) M Aldo. The glucocorticoid receptor an tagonist RU-38486 inhibited both Dex- and Aldo-mediated induction of b eta(1)-mRNA. The mineralocorticoid receptor antagonist spironolactone inhibited Aldo-mediated induction of beta(1)-mRNA, whereas it had no e ffect on Dex-mediated induction of beta(1)-mRNA. Removal of Na+ from t he extracellular medium (isosmotic replacement with choline) caused no effect on Dex-mediated induction of beta(1)-mRNA, whereas it inhibite d Aldo-mediated induction of beta(1)-mRNA. Addition of a specific inhi bitor of the Na+/H+ exchange, ethylisopropylamiloride, had no effect o n Dex-mediated induction of beta(1)-mRNA, whereas it resulted in a sig nificant inhibition of Aldo-mediated induction of beta(1)-mRNA. We con clude that 1) both Dex and Aldo induce Na+-K+-ATPase alpha(1)- and bet a(1)-mRNA expression in a time- and dose-dependent manner; 2) Dex-medi ated induction of beta(1)-mRNA occurs only through glucocorticoid rece ptors, whereas Aldo-mediated induction of beta(1)-mRNA occurs through both gluco- and mineralocorticoid receptors; and 3) Dex-mediated induc tion of beta(1)-mRNA occurs through Na+-independent mechanisms, wherea s Aldo-mediated induction of beta(1)-mRNA, at least in part, occurs th rough Na+-dependent mechanisms, including stimulation of the Na+/H+ ex change.