Nongenomic effect of aldosterone on Na+,K+-adenosine triphosphatase in arterial vessels.

Aldosterone increases Na(+),K(+)-adenosine triphophatase (Na(+),K(+)-ATPase) pump activity and abundance under chronic conditions in several tissues, including rat arterial vessels. The present study was undertaken to evaluate whether aldosterone has also short-term effects on the Na(+),K(+)-ATPase of rat aorta. The pump function was measured as ouabain-sensitive (86)Rb/K uptake in aortic rings. Addition of aldosterone induced a rapid inhibition of the Na(+),K(+)-ATPase (57.0 +/- 2.3% of control values; P < 0.05; n = 8), followed by a return to control values after 120 min. The aldosterone-induced decrease in ouabain-sensitive (86)Rb/K uptake was prevented by the new mineralocorticoid receptor antagonist eplerenone. The inhibition of gene transcription (actinomycin D) or protein synthesis (cycloheximide) had no effect on short-term aldosterone action on Na(+),K(+)-ATPase. The rapid aldosterone inhibition was also observed in the presence of monensin, a sodium-specific ionophore. Rapamycin, an immunosuppressive drug that stabilizes the heat shock protein-steroid receptor complex, blocked the rapid aldosterone effect. Bisindole I, an inhibitor of protein kinase C, also blocked nongenomic action of aldosterone on the Na pump. The nongenomic effect of aldosterone was inhibited by disrupters of microtubule (colchicine). Plasma membrane protein biotinylation of aortic segments and Western blot indicated a diminished presence of catalytic isoforms of Na(+),K(+)-ATPase on the cell surface. Our findings indicate that aldosterone has a nongenomic effect on the Na(+),K(+)-ATPase of vascular tissue. This effect is mediated through protein kinase C activation and implies reduced cell surface abundance of catalytic subunits. These observations together with our previous report on chronic hormone replacement suggest that aldosterone is directly involved in ionic cellular homeostasis of the vascular system through Na pump regulation.