[Effects of leukotriene receptor antagonists on vascular endothelial growth factor and its receptors in a sensitized rat model].

Abstract

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.

• Authors: Hong-Shen Yang, Lai Wang, Wei Yang, Ji-Tao Guan, Jun-Yi Ma, Yan Su
• Journal: Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases (Zhonghua Jie He He Hu Xi Za Zhi) Vol. 32 Issue 3 Pg. 177-81 (Mar 2009) ISSN: 1001-0939 [Print] China
• PMID: 19575935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetates
• Cyclopropanes
• Leukotriene Antagonists
• Quinolines
• Sulfides
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Leukotriene D4
• Receptors, Vascular Endothelial Growth Factor
• montelukast

Topics

• Acetates (pharmacology, therapeutic use)
• Airway Remodeling
• Animals
• Asthma (drug therapy, metabolism)
• Cyclopropanes
• Leukotriene Antagonists (pharmacology, therapeutic use)
• Leukotriene D4 (blood)
• Male
• Neovascularization, Pathologic
• Quinolines (pharmacology, therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptors, Vascular Endothelial Growth Factor (metabolism)
• Sulfides
• Vascular Endothelial Growth Factor A (blood, metabolism)