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Research Article Free access | 10.1172/JCI119451

Nitric oxide synthase lies downstream from vascular endothelial growth factor-induced but not basic fibroblast growth factor-induced angiogenesis.

M Ziche, L Morbidelli, R Choudhuri, H T Zhang, S Donnini, H J Granger, and R Bicknell

Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Department of Pharmacology, University of Florence, 50134, Florence, Italy. ziche@stat.ds.unifi.it

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Published June 1, 1997 - More info

Published in Volume 99, Issue 11 on June 1, 1997
J Clin Invest. 1997;99(11):2625–2634. https://doi.org/10.1172/JCI119451.
© 1997 The American Society for Clinical Investigation
Published June 1, 1997 - Version history
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Abstract

Systemic administration of the nitric oxide (NO) synthase inhibitor Nomega-nitro--arginine methyl ester (L-NAME) to rabbits bearing a corneal implant blocked vascular endothelial growth factor (VEGF), but not basic fibroblast growth factor (bFGF)-induced angiogenesis. L-NAME completely blocked angiogenesis induced by VEGF-transfected MCF-7 breast carcinoma cells and the cells remained dormant in the cornea. Postcapillary endothelial cell migration and growth induced by VEGF were blocked by both the NO synthase inhibitor Nomega-mono-methyl--arginine and by the guanylate cyclase inhibitor LY 83583. We conclude that NO is a downstream imperative of VEGF-, but not bFGF-induced angiogenesis, and propose that the NO synthase/guanylate cyclase pathway is a potential target for controlling tumor angiogenesis in response to VEGF. Our studies support recent evidence that VEGF and bFGF induce angiogenesis by different mechanistic pathways using the alphavbeta5 and alphavbeta3 integrins, respectively.

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