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PMID: 9169492 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 99 ·No. 11 ·1997-06-01 ·Pages 2625-34

Ziche M, Morbidelli L, Choudhuri R, Zhang HT, Donnini S, Granger HJ, Bicknell R

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.

MeSH Terms
Animals Cornea/blood supply Corneal Transplantation Endothelial Growth Factors/physiology Enzyme Inhibitors/administration & dosage Fibroblast Growth Factor 2/physiology Lymphokines/physiology NG-Nitroarginine Methyl Ester/administration & dosage Neovascularization, Physiologic/drug effects,physiology Nitric Oxide Synthase/antagonists & inhibitors,physiology Rabbits Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Endothelial Growth Factors Enzyme Inhibitors Lymphokines Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Fibroblast Growth Factor 2 Nitric Oxide Synthase NG-Nitroarginine Methyl Ester
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Ziche M
Department of Pharmacology, University of Florence, 50134, Florence, Italy. [email protected]
Morbidelli L
Choudhuri R
Zhang H T
Donnini S
Granger H J
Bicknell R
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI119451
Email
[email protected]
Published
1997-06-01
Pages
2625-34
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC508108
Subset
IM
Corrections
CommentIn
PMID: 11306596
External Links
PubMed source DOI: 10.1172/JCI119451 PMC Full Text View journal details
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