REGULATION OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE MESSENGER-RNA, PROTEIN, AND ACTIVITY DURING CELL-GROWTH

Cell growth influences the expression of several important tissue-spec ific functions. We sought to examine the effect of cell proliferation on nitric oxide (NO) synthase gene expression in cultured aortic bovin e endothelial cells. Western and Northern blot analysis revealed three - and sixfold increases in NO synthase protein and mRNA, respectively, in growing compared with growth-arrested cells. The release of nitrog en oxides was also increased in proliferating cells compared with grow th-arrested cells, as was the NO synthase activity assessed by L-argin ine/L-citrulline conversion. Neither NO synthase inhibitors nor supero xide dismutase affected proliferation or thymidine incorporation, sugg esting that increased NO release had no effect on endothelial cell gro wth. In conclusion, these studies demonstrate that expression of endot helial cell NO synthase is markedly increased in proliferating compare d with quiescent nongrowing cells. The mechanisms underlying this and its physiological consequences remain to be defined.