Low concentrations of ouabain induce vascular smooth muscle cell proliferation

Ouabain is a well known inhibitor of the Na+ pump in all mammalian cells. W e have demonstrated that ouabain at concentrations below those which inhibi t the pump, i.e. 0.1 nM and 1.0 nM, induce proliferation of saphenous vein smooth muscle cells as measured by bromodeoxyuridine (BrdU) uptake. Ouabain at these low concentrations also activated MAPK. Proliferating concentrati ons of the drug did not increase levels of Ca-i(2+), suggesting no effect o f this ion in the process. In addition, incubation of the cells in low leve ls of K+, which has been shown to inhibit the pump, had no effect on prolif eration. These data show that low concentrations of ouabain that do not inh ibit the Na+ puump can activate proliferation of vascular smooth muscle cel ls, suggesting that the pump complex may act as a transducing receptor.