Felodipine attenuates vascular inflammation in a fructose-induced rat model of metabolic syndrome via the inhibition of NF-kappaB activation.
OBJECTIVE
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).


METHODS
Male Wistar rats were given 10% fructose in drinking water. After 32 weeks of high fructose feeding, they were treated with felodipine (5 mg x kg(-1) x 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-kappaB activity was measured by electrophoretic mobility shift assay (EMSA).


RESULTS
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-kappaB. 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-kappaB activation in FFR.


CONCLUSIONS
Felodipine inhibited vessel wall inflammation. The inhibition of NF-kappaB may be involved in the modulation of vascular inflammatory response by CCB in metabolic syndrome.
Tan
Hong-wei
HW
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Ji-nan 250012, China.
Xing
Shan-shan
SS
Bi
Xiu-ping
XP
Li
Li
L
Gong
Hui-ping
HP
Zhong
Ming
M
Zhang
Yun
Y
Zhang
Wei
W
D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002784:Cholesterol / Q000097:blood; D015736:Felodipine / Q000494:pharmacology*; D005632:Fructose; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000473:pathology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014657:Vasculitis / Q000139:chemically induced / Q000473:pathology*
D001786:Blood Glucose; D002121:Calcium Channel Blockers; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D005632:Fructose; D002784:Cholesterol; D015736:Felodipine