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

Abstract

ABSTRACT-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-a (TNF-a ) and interleukin-1b (IL-1b) formation and iNOS induction both in lipopolysaccharide (LPS) and interferon-g (IFN-g)-treated rat aortic smooth muscle cells (RASMC) and in a rat model of endotoxemia. Incubation with amlodipine (0.1 -10 m M) for 24 h resulted in a significant and dose-dependent attenuation in medium nitrite, TNF-a and IL-1b formation as well as iNOS protein expression in LPS /IFN-g -treated RASMC. In addition, amlodipine inhibited leucigenin-induced superoxide formation in RASMC. In the rat endotoxic model, the serum nitrite /nitrate, TNF-a and IL-1b levels as well as iNOS protein expression of lungs were also suppressed by administration of amlodipine (50 m g/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.

Effects of hypertension and ovariectomy on rat hepatocytes. Are amlodipine and lacidipine protective? (A stereological and histological study)

“…Recent studies have also indicated that amlodipine increases the bioavailability of endothelial NO and that the increased eNO has antioxidant properties. Furthermore, it has been shown that amlodipine suppresses proinflammatory cytokines and ROS (38)(39)(40). In the present study, both amlodipine and lacidipine were effective in ameliorating the decreases in hepatocyte number caused by either hypertension or postmenopausal period aging.…”

Amlodipine inhibits TNF-α production and attenuates cardiac dysfunction induced by lipopolysaccharide involving PI3K/Akt pathway

“…In addition, reduction of extracellular calcium with EGTA had only a minor effect on the expression of iNOS induced by LPS [46]. These evidence indicated that DHP-type CCBs' immunosuppressive activities might be independent of their calcium channel blocking activities [51,52]. Umemoto et al [53] have demonstrated that amlodipine inhibited TNF-α and iNOS expression in LPS-stimulated vascular smooth muscle cells.…”

Potential role of the cardiovascular non-antibiotic (helper compound) amlodipine in the treatment of microbial infections: scope and hope for the future

“…Similarly, in the rat endotoxic model, serum nitrite/nitrate concentrations, TNF␣ and IL-1␤ levels as well as iNOS expression in the lungs were also suppressed by administration of AML. The drug has been shown to prevent lowering of vascular responsiveness induced by injection of Salmonella typhosa LPS [59,60].…”