Skip Navigation

Cardiovascular Research 1997 36(2):276-281; doi:10.1016/S0008-6363(97)00177-6
© 1997 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Malavaud, B.
Right arrow Articles by Plouët, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malavaud, B.
Right arrow Articles by Plouët, J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1997, European Society of Cardiology

Activation of Flk-1/KDR mediates angiogenesis but not hypotension

Bernard Malavauda,b, Ivan Tackc, Frédéric Joncaa,b, Françoise Praddaudec, Françoise Moroa, Jean-Louis Aderc and Jean Plouëta,*

aLaboratoire de Biologie Moléculaire Eucaryote/UPR CNRS 9006, 118 route de Narbonne, 31062 Toulouse Cedex, France
bService d'Urologie, CHU Purpan — Faculté de Médecine, 31062 Toulouse Cedex, France
cLaboratoire de Physiologie/Unité INSERM 388 31062 Toulouse Cedex, France

* Corresponding author. Tel. (+33–5) 61335826; Fax (+33–5) 61335886.

Objective: The concept of therapeutic angiogenesis with vascular endothelial growth factor (VEGF) has been validated in peripheral arterial disease. Its use in myocardial ischemia may be delayed as the result of the description in a porcine model of peripheral vasodilation after intraluminal injections of VEGF resulting in a 50% fatality rate by hypotension. We carried out this study to test whether VEGF-induced hypotension (1) is species specific, (2) is mediated by the receptor mediating angiogenesis, (3) is prevented by inhibition of nitric oxide synthase. Methods: In the rabbit corneal pocket assay we tested whether a previously published anti-idiotypic antibody (AIA) agonist of the VEGF receptor Flk-1/KDR could elicit angiogenesis. Various doses of recombinant VEGF or AIA were injected into anesthetized normotensive Wistar–Kyoto rats and the mean arterial blood pressure (MABP) was recorded. To test the implication of nitric oxide in VEGF-induced hypotension we treated the animals with a competitive inhibitor of nitric oxide synthase prior to the injection of VEGF. Results: Both VEGF and AIA induce angiogenesis but only intravenous injections of VEGF induced a rapid, transient and dose-dependent decrease in MABP. The ED50 was 0.5 µg. The interval between two VEGF injections required to lead to a decrease of MABP was 40 minutes. Nitric oxide synthesis inhibitor prevented, in a reversible fashion, the effect of VEGF. Conclusion: VEGF-induced hypotension is not species specific. It is prevented by nitric oxide inhibition. VEGF-induced angiogenesis and hypotension are not mediated in vivo by the same VEGF receptor

KEYWORDS Angiogenesis; Blood pressure; Vascular endothelial growth factor; Flk-1/KDR; Flt-1; Nitric oxide; Wistar–Kyoto rat; Rabbit


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.