MECHANISMS OF NITROSOTHIOL-INDUCED ANTIMITOGENESIS IN AORTIC SMOOTH-MUSCLE CELLS

The purpose of this work was to investigate the effect of a nitrosothiol vasodilator, S-nitroso-N-acetylpenicillamine (SNAP), on serum-induced cell proliferation, thymidine uptake, RNA synthesis, protein synthesis and thymidine kinase activity in a cultured rat aortic smooth muscle cell line. SNAP decreased the rate of serum-stimulated cell proliferation, thymidine uptake and incorporation, uridine and leucine incorporation and thymidine kinase activity in concentration-dependent fashion. The threshold concentration of SNAP for inhibition of cell proliferation and thymidine uptake was similar and in the range of 1-3 muM. Uridine incorporation, indicative of RNA synthesis, was inhibited beginning at 10 muM SNAP, whereas leucine incorporation, indicative of protein synthesis, and thymidine kinase activity, an enzyme of importance to DNA synthesis, were inhibited beginning at 100 muM SNAP. These results indicate that inhibition of cell proliferation induced by relatively low concentrations of SNAP (1-10 muM) is independent of inhibition of protein synthesis or thymidine kinase activity, whereas higher concentrations of SNAP may inhibit cell proliferation by decreasing protein synthesis.