OUABAIN ENHANCES THE MITOGENIC EFFECT OF SERUM IN VASCULAR SMOOTH-MUSCLE CELLS

Recently ouabain has been shown to induce transcription of proto-oncog enes in different cell types. In the present study, we examined the ef fect of ouabain on the proliferation of cultured vascular smooth muscl e cells (VSMCs). Primary aortic VSMCs of spontaneously hypertensive (S HR) and Wistar Kyoto (WKY) rats, and the rat VSMC cell line A10, were used. Different concentrations of ouabain (10(-9) to 10(-5) mol/L) wer e added to either quiescent or proliferating cells, and the cell numbe r, the rate of thymidine incorporation into DNA, and the transcription of c-fos and c-myc were examined. The addition of ouabain to prolifer ating VSMC increased the rate of thymidine incorporation into DNA in a dose-dependent manner, and induced the transcription of the proto-onc ogenes within 1 h. This latter response disappeared after 24 h. The nu mber of cells significantly increased in response to low concentration s of ouabain (10(-8) to 10(-7) mol/L), but gradually decreased in resp onse to higher concentrations of the agent, probably due to a toxic ef fect. Addition of ouabain to quiescent cells, in medium without serum, did not promote cell growth by any of the parameters examined. Accord ing to a current theory, endogenous digitalis-like substances possess natriuretic and hypertensive properties, and provide the link between an excessive intake of salt and high blood pressure. The mitogenic eff ect of ouabain on VSMCs may be a component of this hypertensive action .