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

Cell growth influences the expression of several important tissue-specific functions. We sought to examine the effect of cell proliferation on nitric oxide (NO) synthase gene expression in cultured aortic bovine 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 nitrogen oxides was also increased in proliferating cells compared with growth-arrested cells, as was the NO synthase activity assessed by L-arginine/L-citrulline conversion. Neither NO synthase inhibitors nor superoxide dismutase affected proliferation or thymidine incorporation, suggesting that increased NO release had no effect on endothelial cell growth. In conclusion, these studies demonstrate that expression of endothelial cell NO synthase is markedly increased in proliferating compared with quiescent nongrowing cells. The mechanisms underlying this and its physiological consequences remain to be defined.