Effect of vascular endothelial growth factor on nasal vascular permeability.
OBJECTIVE
One of the major functions of vascular endothelial growth factor (VEGF) is increasing vascular permeability. We previously reported that VEGF is present in nasal secretions in rhinosinusitis, particularly in allergic rhinitis, and is hyperproduced immediately after antigen provocation. However, its function in nasal mucosa has not yet been investigated. This study was designed to estimate the increased vascular permeability by VEGF in nasal mucosa and to discuss its possible role in allergic rhinitis.


METHODS
Prospective animal experiment.


METHODS
Hartley guinea pigs were used. Ethyl carbamate was injected into the abdomen for anesthesia, followed by intravenous injection of Evans blue into the femoral vein. Phosphate buffered saline, histamine, or VEGF was then applied to nasal cavities. Nasal mucosa was harvested after saline reflux from heart with phlebotomy by amputating the abdominal aorta. Tissue samples were soaked in formamide for 12 hours at 63 degrees C to extract dye exudates from nasal mucosa. To analyze vascular permeability, dye was quantified by colorimetry.


RESULTS
VEGF increased vascular permeability in nasal mucosa, and was more than 1 x 10(6) times more potent than histamine on the basis of molar units. Although increased vascular permeability by VEGF was not inhibited by histamine 1 receptor antagonist, it was markedly inhibited by anti-VEGF receptor antibodies.


CONCLUSIONS
VEGF increased vascular permeability to a greater degree than histamine in nasal mucosa via a different pathway. Regulating VEGF may be a new therapeutic option for persistent nasal symptoms in allergic rhinitis.
Matsune
Shoji
S
Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan. shoji@m2.kufm.kagoshima-u.ac.jp
Ohori
Junichiro
J
Yoshifuku
Kousuke
K
Kurono
Yuichi
Y
D000281:Administration, Intranasal; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003124:Colorimetry; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D009297:Nasal Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D011446:Prospective Studies; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000493:pharmacokinetics*
D006634:Histamine H1 Antagonists; D042461:Vascular Endothelial Growth Factor A