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 microgram/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 micrograms/ml) or actinomycin D (5 micrograms/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).