Nitric oxide mediates angiogenesis induced in vivo by platelet-activating factor and tumor necrosis factor-alpha.
We evaluated the role of an endogenous production of nitric oxide (NO) in the in vitro migration of endothelial cells and in the in vivo angiogenic response elicited by platelet-activating factor (PAF), tumor necrosis factor-alpha (TNF), and basic fibroblast growth factor (bFGF). The NO synthase inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), but not its enantiomer D-NAME, prevented chemotaxis of endothelial cells induced in vitro by PAF and by TNF. The motogenic activity of TNF was also inhibited by WEB 2170, a specific PAF-receptor antagonist. In contrast, chemotaxis induced by bFGF was not prevented by L-NAME or by WEB 2170. Angiogenesis was studied in vivo in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model, the angiogenesis induced by PAF and TNF was inhibited by WEB 2170 and L-NAME but not by D-NAME. In contrast, angiogenesis induced by bFGF was not affected by L-NAME or by WEB 2170. TNF, but not bFGF, induced PAF synthesis within Matrigel. These results suggest that NO mediates the angiogenesis induced by PAF as well as that induced by TNF, which is dependent on the production of PAF. In contrast, the angiogenic effect of bFGF appears to be both PAF and NO independent.
Montrucchio
G
G
Dipartimento di Fisiopatologia Clinica, Università di Torino, Italy.
Lupia
E
E
de Martino
A
A
Battaglia
E
E
Arese
M
M
Tizzani
A
A
Bussolino
F
F
Camussi
G
G
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D001381:Azepines; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C063964:bepafant; D019331:NG-Nitroarginine Methyl Ester