Metabolic syndrome is associated with an increased incidence of atherosclerosis. Clinical studies have shown that calcium channel blockers (CCB) inhibit the progression of atherosclerosis. However, the underlying mechanism is unclear. We investigated the inhibitory effect of felodipine on adhesion molecular expression and macrophage infiltration in the aorta of high fructose-fed rats (FFR).
Male Wistar rats were given 10% fructose in drinking water. After 32 weeks of high fructose feeding, they were treated with felodipine (5 mg·kg-1·d-1) for 6 weeks. The control rats were given a normal diet and water. The aortic expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and the infiltration of macrophages were measured by real-time RT-PCR and/or immunohistochemistry. NF-κB activity was measured by electrophoretic mobility shift assay (EMSA).
After 32 weeks of high fructose feeding, FFR displayed increased body weight, systolic blood pressure (SBP), serum insulin, and triglycerides when compared with the control rats. The aortic expressions of ICAM-1 and VCAM-1 were significantly increased in FFR than in the control rats and accompanied by the increased activity of NF-κB. FFR also showed significantly increased CD68-positive macrophages in the aortic wall. After treatment with felodipine, SBP, serum insulin, and the homeostasis model assessment decreased significantly. In addition to reducing ICAM-1 and VCAM-1, felodipine decreased macrophages in the aortic wall. EMSA revealed that felodipine inhibited NF-κB activation in FFR.
Felodipine inhibited vessel wall inflammation. The inhibition of NF-κB may be involved in the modulation of vascular inflammatory response by CCB in metabolic syndrome.
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This study was supported by research funding by AstraZeneca Pharmaceutical Co Ltd China (QD02 to Dr Wei ZHANG) and by the National Natural Science Foundation of China (No 30670874 to Dr Wei ZHANG).
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Tan, Hw., Xing, Ss., Bi, Xp. et al. Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-κB activation. Acta Pharmacol Sin 29, 1051–1059 (2008). https://doi.org/10.1111/j.1745-7254.2008.00843.x
- calcium channel blocker
- fructose-fed rat
- metabolic syndrome
- adhesion molecule
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