Amlodipine Inhibits Pro-inflammatory Cytokines and Free Radical Production and Inducible Nitric Oxide Synthase Expression in Lipopolysaccharide/Interferon-γ-Stimulated Cultured Vascular Smooth Muscle Cells

The Japanese Journal of Pharmacology

Dee Pei¹  Tz-Chong Chou²  Shih-Ping Yang³ 

[1] Division of Endocrinology and Metabolism, Tri-Service General Hospital;Graduate Institute of Medical Sciences, National Defense Medical Center;Division of Cardiology, Tri-Service General Hospital

关键词: Amlodipine;    Inducible nitric oxide synthase;    Lipopolysaccharide;    Cytokine;    Free radical;   

DOI  :  10.1254/jjp.89.157

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(32)Cited-By(17)Overproduction of nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is importantly involved in the pathogenesis of endotoxemia and atherosclerosis. Calcium antagonists are commonly used as cardiovascular drugs and have a beneficial effect on prolonging survival in various models of endotoxin shock. The present study was to investigate the effect of a calcium antagonist amlodipine on nitrite, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) formation and iNOS induction both in lipopolysaccharide (LPS) and interferon-γ (IFN-γ)-treated rat aortic smooth muscle cells (RASMC) and in a rat model of endotoxemia. Incubation with amlodipine (0.1 – 10 μM) for 24 h resulted in a significant and dose-dependent attenuation in medium nitrite, TNF-α and IL-1β formation as well as iNOS protein expression in LPS/IFN-γ-treated RASMC. In addition, amlodipine inhibited leucigenin-induced superoxide formation in RASMC. In the rat endotoxic model, the serum nitrite/nitrate, TNF-α and IL-1β levels as well as iNOS protein expression of lungs were also suppressed by administration of amlodipine (50 μg/kg, i.v.). These results suggest that amlodipine may exert vascular beneficial effects by suppressing pro-inflammatory cytokines and free radical generation as well as iNOS induction in smooth muscle cells during activation of inflammatory mechanism.

【 授权许可】

Unknown