Basic fibroblast growth factor increases nitric oxide synthase
production in bovine endothelial cells.
Kostyk, S. K., S. Kourembanas, E. L. Wheeler, D. Medeiros, L. P.
McQuillan, P. A. D'amore, and S. J. Braunhut.
Departments of Surgical Research, and Joint Program in Neonatology,
Children's Hospital, and Harvard Medical School, Boston, MA 02115,
Neurology Service, Massachusetts General Hospital, Boston, MA 02114,
Department of Biological Sciences, University of Massachusetts,
Lowell MA 01854
APStracts 2:0191H, 1995.
Basic fibroblast growth factor (bFGF) and nitric oxide (NO) are
expressed by endothelial cells (EC) and are involved in regulation of
endothelial functions. In vivo, bFGF has a hypotensive effect which
is mediated, in part, through activation of nitric oxide synthase
(NOS) and the subsequent generation of NO. Thus, we hypothesized that
regulation of NOS in EC might be modulated by bFGF. Basic FGF
treatment of EC in vitro resulted in increase[delta] NADPH-diaphorase
staining, a histochemical marker associated with the presence of NOS.
Using cGMP generation in a reporter cell as a bioassay for NO
release, we demonstrated that bFGF treatment of EC leads to increased
production of biologically active NO. Furthermore, bFGF treatment of
EC resulted in an increase in cellular content 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 NOS is increased
in EC by treatment with bFGF in vitro. These results suggest that
bFGF has potential to regulate vascular tone through the modulation
of levels of endothelial NOS.
Received 25 August 1994; accepted in final form 1 May 1995.
APS Manuscript Number H766-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 9 May 1995.