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J Periodontol. 2009 Sep;80(9):1518-23. doi: 10.1902/jop.2009.080651.

Venodilatory effect of vascular endothelial growth factor on rat gingiva.

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Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary.



Endothelial cell proliferation, angiogenesis, and increased vascular permeability are among the effects of vascular endothelial growth factor (VEGF) in various organs. However, the effects of VEGF on gingival hemodynamics, especially on venules, have not been thoroughly investigated. This study investigated the acute circulatory effects of VEGF on rat gingival venules.


Fifty-six anesthetized rats were divided into five study groups; each rat received 10 microl of experimental solution dripped onto the lower interincisal gingiva. The groups included: 1) saline control (after the experiment, gingiva was excised for VEGF receptor 2 [VEGFR2] immunohistochemistry); 2) VEGF (0.1, 1, 10, or 50 microg/ml); 3) VEGF2 receptor antagonist 5-((7-benzyloxyquinazolin-4-yl)amino)-4-fluoro-2-methyl-phenol-hydrochloride (ZM323881; 20 microg/ml); 4) ZM323881 (20 microg/ml) followed by VEGF application (50 microg/ml after 15 minutes); and 5) VEGF (10 microg/ml), these rats were premedicated with nitric oxide (NO) synthase blocker (N(G)-nitro-L-arginine-methyl-ester [L-NAME]; 1 mg/ml in drinking water) for 1 week before the experiment. Changes in gingival superficial venule diameter were measured by vital microscopy prior to and 1, 5, 15, 30, and 60 minutes after the administration of the experimental solutions.


VEGF dose-dependently increased the venular diameter compared to saline. ZM323881 alone did not cause any alteration. Premedication with ZM323881 or L-NAME decreased the dilatory effects of VEGF. VEGFR2 immunohistochemical labeling was observed in the wall of the venules.


There is no remarkable VEGF production under physiologic circumstances in rat gingiva, but VEGF is able to increase gingival blood flow through the activation of VEGF2 receptors. Furthermore, NO release may contribute to VEGF's vasodilatory effect.

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