[Effects of leukotriene receptor antagonists on vascular endothelial growth factor and its receptors in a sensitized rat model].
OBJECTIVE
To investigate the effect of montelukast (MK) on airway inflammation and remodeling in asthmatic rats, and to explore the regulating role of MK on vascular endothelial growth factor (VEGF) and its receptors.


METHODS
Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups, a control group (n = 8), an asthmatic group (n = 8) and a MK treated group (n = 8). The rats were sensitized with ovalbumin and AL (OH3), and repeatedly exposed to aerosolized ovalbumin. Airway reactivity of the animals were measured by animal lung function meter. VEGF levels and leukotriene D(4) (LTD(4)) in serum were measured by enzyme linked-immunosorbent assay (ELISA). The pathologic changes of bronchi and the lung tissue were evaluated, and the expression of VEGF and its acceptors was analyzed with immunohistochemistry. The vascular counts and vascular smooth muscle thickness were measured by using image analysis system.


RESULTS
The bronchial provocation test showed that, in the asthmatic group, the average expiratory resistance increased remarkably. The serum levels of VEGF and LTD(4) in the asthmatic group were 31 +/- 6 and 11 +/- 4 respectively, significantly higher than those in the control group (17 +/- 5 and 6.1 +/- 0.7) respectively and in the MK group (15 +/- 4 and 9.8 +/- 1.6) respectively. (F 63.78, 39.56 all P < 0.01). Immunohistochemistry showed that, the expression of VEGF, VEGFR(1) and VEGFR(2) in the asthmatic group were increased, as compared to those in the control group and the treated group. The vascular counts were 14 +/- 2, 22 +/- 2 and 16 +/- 4 in the control, the asthmatic, and the treated groups.


CONCLUSIONS
VEGF and its receptors were over-expressed in the sensitized rat model, and involved in angiogenesis and airway remodeling. MK may be effective in reducing allergic airway inflammation and airway remodeling through VEGF and VEGFR.
Yang
Hong-Shen
HS
Department of Respirology, the Second Affiliated Hospital of Hebei Medical University, Shijiazhuang 050000, China. yhs4546@sohu.com.cn
Wang
Lai
L
Yang
Wei
W
Guan
Ji-Tao
JT
Ma
Jun-Yi
JY
Su
Yan
Y
D000085:Acetates / Q000494:pharmacology* / Q000627:therapeutic use; D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism*; D003521:Cyclopropanes; D020024:Leukotriene Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D017998:Leukotriene D4 / Q000097:blood; D008297:Male; D009389:Neovascularization, Pathologic; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism*
D000085:Acetates; D003521:Cyclopropanes; D020024:Leukotriene Antagonists; D011804:Quinolines; D013440:Sulfides; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D017998:Leukotriene D4; D040262:Receptors, Vascular Endothelial Growth Factor; C093875:montelukast