BASIC FIBROBLAST GROWTH-FACTOR INCREASES NITRIC-OXIDE SYNTHASE PRODUCTION IN BOVINE ENDOTHELIAL-CELLS

Basic fibroblast growth factor (bFGF) and nitric oxide (NO) are expres sed by endothelial cells (EC) and are involved in regulation of endoth elial functions. In vivo, bFGF has a hypotensive effect which is media ted, in part, through activation of nitric oxide synthase (NOS) and th e subsequent generation of NO. Thus we hypothesized that regulation of NOS in EC might be modulated by bFGF. bFGF treatment of EC in vitro r esulted in increased NADPH diaphorase staining, a histochemical marker associated with the presence of NOS. Using cGMP generation in a repor ter cell as a bioassay for NO release, we demonstrated that bFGF treat ment of EC leads to increased production of biologically active NO. Fu rthermore, bFGF treatment of EC resulted in an increase in cellular co ntent of the endothelial form of NOS as shown by Western blot analysis . Finally, Northern blot analysis was used to demonstrate that message levels of the constitutive, calcium-dependent, endothelial form of NO S is increased in EC by treatment with bFGF in vitro. These results su ggest that bFGF has potential to regulate vascular tone through the mo dulation of levels of endothelial NOS.