Knockout mice for bFGF (basic fibroblast growth factor) show reduced systemic blood pressure (Dono et al. 1998). The reason for that, however, is not completely understood so far. We hypothesized that nitric oxide (NO) plays a modulator role in angiogenesis and vascular remodeling by interactions with growth factors and investigated therefore the interplay of NO with bFGF and VEGF (vascular endothelial cell growth factor), both cytokines known for their potency in vascular remodelling and angiogenesis and additionally investigated possible modulator effects of both, bFGF and VEGF, on NO synthesis as possible feedback loop. Primary endothelial cells (HUVEC) were used throughout the study. VEGF (5-10ng/ml) or histamine (1μg/ml), used here as independent control, induced NO production after 6h (measured as NO₂ (nitrite) 3-fold vs. control, n=8, p<0.05) significantly, whereas bFGF (3ng/ml) had no inductor effect. Furthermore, bFGF even inhibited NO production when it was combined with VEGF or histamine. These bFGF effects were abolished by a bFGF receptor antagonist or wortmannin, indicating a PI3Kinase-dependent signalling pathway. Similarly, in shear stress experiments (16dyn/cm²) the addition of bFGF receptor blockers led to an exponential increase in shear stress induced NO formation indicating, again, a bFGF-dependent inhibition of mechanically induced NO formation. The inhibitory effects of bFGF and the inductive effects of VEGF on the NO production were also reflected by their individual interplay with NO. Exogenously added NO (S-nitroso-N-acetyl-D,L penicillamine, SNAP, 1μM,) inhibited bFGF-induced migration by 50% but not the VEGF-induced (n=4×10, p<0.05). Accordingly, bFGF-induced differentiation (capillary-like structure formation from aortic rings) was increased 2-fold if basal NO production was inhibited (L-NA (L-nitro-arginine), 30μM) whereas the effect of VEGF on vessel sprouting was reduced by 50%. Similar effects were found in proliferation in which VEGF- but not bFGF-induced cell growth was reduced by L-NA (14% after 72h, n=8, p<0.05). The results identify NO as a significant modulator of vascular remodelling and angiogenesis by affecting the efficiency of the growth factors VEGF and bFGF in an opposed manner. Moreover, bFGF-dependent inhibition of NO production might be a set back mechanism for flow-induced NO production. By that, bFGF prevents an overshoot in dilatation and may participate in local blood pressure regulation.