REGULATION OF NA-K-ATPASE GENE-EXPRESSION BY ANGIOTENSIN-II IN VASCULAR SMOOTH-MUSCLE CELLS

Na-K-adenosinetriphosphatase (Na-K-ATPase) activity profoundly influences vascular cell excitability, contractility, and volume regulation. We investigated the effect of angiotensin II on Na-K-ATPase gene expression in cultured rat vascular smooth muscle cells (VSMC). Na-K-ATPase alpha(1)- and beta 1-isoform mRNAs, but not alpha(2)- and alpha 3-isoform mRNAs, were expressed in cultured rat VSMC. Angiotensin II (1 mu g/ml) caused a threefold increase in alpha(1)-mRNA accumulation and a fourfold increase in beta(1)-mRNA accumulation; the peak increases for both alpha(1)- and beta(1)-mRNA were observed at 6 h. Angiotensin II induced alpha(1)- and beta(1)-mRNA expression in a dose-dependent manner. Pretreatment of VSMC with cycloheximide (20 mu g/ml) or actinomycin D (5 mu g/ml) completely inhibited angiotensin II-induced alpha(1)-mRNA accumulation. Even after protein kinase C (PKC) activity was functionally depleted by treating VSMC with phorbol 12-myristate 13-acetate (10(-6) M) for 24 h, angiotensin II increased alpha(1)-mRNA accumulation, The angiotensin II-induced increase in alpha(1)-mRNA accumulation was associated with an increase in alpha(1)-subunit protein accumulation. These results indicate that angiotensin II stimulates Na-K-ATPase alpha(1)- and beta 1-isoform gene expression in VSMC and that the effect is mediated not via activation of PKC but needs synthesis of intermediate regulatory protein(s).