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This Article Full Text Full Text (PDF) All Versions of this Article: 572/1/243    most recent jphysiol.2005.103127v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Glass, C. A. Articles by Bates, D. O. Search for Related Content PubMed PubMed Citation Articles by Glass, C. A. Articles by Bates, D. O. Related Collections Cardiovascular

¹ Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, Southwell Street, University of Bristol, Bristol BS2 8EJ, UK

Vascular endothelial growth factor (VEGF) is the principal agent that increases microvascular permeability during physiological and pathological angiogenesis. VEGF is differentially spliced to form two families of isoforms: VEGF_xxx, and VEGF_xxxb. Whereas VEGF₁₆₅ stimulates angiogenesis, VEGF₁₆₅b is anti-angiogenic. To determine the effect of VEGF₁₆₅b on permeability, hydraulic conductivity (L_p) was measured in individually perfused microvessels in the mesentery of frogs and rats. As with VEGF₁₆₅, VEGF₁₆₅b increased L_p in amphibian (2.4 ± 0.3-fold) and mammalian (1.9 ± 0.2-fold) mesenteric microvessels. A dose–response relationship showed that VEGF₁₆₅b (EC₅₀, 0.65 pM) was approximately 25 times more potent than VEGF₁₆₅ (EC₅₀, 16 pM) in amphibian microvessels. VEGF₁₆₅ has been shown to increase permeability through VEGF receptor 2 (VEGF-R2) signalling. However, VEGF₁₆₅b increased L_p of frog vessels to the same extent in the presence of the VEGF-R2 inhibitor ZM323881, indicating that it does not increase permeability via VEGF-R2 signalling, and was inhibited by the VEGF receptor inhibitor SU5416 at doses that are specific for VEGF receptor 1 (VEGF-R1). VEGF₁₆₅b, in contrast to VEGF₁₆₅, did not result in a sustained chronic increase in L_p. These results show that although VEGF₁₆₅b is anti-angiogenic in the mesentery, it does signal in endothelial cells in vivo resulting in a transient, but not sustained, increase in microvascular L_p, probably through VEGF-R1.

(Received 6 December 2005; accepted after revision 18 January 2006; first published online 19 January 2006)
Corresponding author D. Bates: Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, Southwell Street, University of Bristol, Bristol BS2 8EJ, UK. Email: dave.bates{at}bristol.ac.uk

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