Mice lacking bFGF show reduced systemic blood pressure. We hypothesized that nitric oxide (NO) plays a modulator role by interactions with growth factors and investigated therefore the interplay of NO with bFGF and VEGF and additionally possible feedback effects of both, bFGF and VEGF, on NO formation.

Results: VEGF induced NO formation in aortic endothelial cells significantly (n=8, p<0.05), whereas bFGF had no inductor effect. Combined with VEGF, bFGF even inhibited NO production. This effect was abolished by bFGF blockade and wortmannin, indicating a PI3-Kinase-dependent signaling. Shear stress increased NO production only transiently, however, blockade of the bFGF receptor led to a steady NO formation indicating bFGF- dependent inhibited NO-formation. The antagonistic effects of bFGF and VEGF on NO formation were reflected by a feed back of NO. Added NO (SNAP) inhibited bFGF-induced migration but not those induced by VEGF (n=4x10, p<0.05). Likewise lack of NO led to reduced VEGF- and increased bFGF-induced formation of capillary like structures.

Conclusion: NO is a significant modulator of vascular remodelling and angiogenesis by affecting the efficiency of VEGF and bFGF in an oppositional manner. Moreover, release of bFGF might be a set back mechanism for flow induced NO production. By that, bFGF might be part of a negativ feed back loop in local blood pressure regulation.