Abstract
Neutrophils play an important role in the progression of atherosclerosis in concert with proinflammatory cytokines. Calcium channel blockers are commonly used for treatment of hypertension, and their pleiotropic effects other than lowering blood pressure are recently recognized. We studied the effects of various calcium channel blockers (amlodipine, nicardipine, cilnidipine, benidipine, efonidipine, nifedipine, azelnidipine, verapamil, and diltiazem) on superoxide (ROS) release, migration, and the signaling pathways in human neutrophils stimulated by GM-CSF or TNF. GM-CSF-induced ROS release was suppressed by amlodipine, nicardipine, and cilnidipine, whereas TNF-induced ROS release was suppressed by amlodipine, nicardipine, cilnidipine, benidipine, efonidipine, nifedipine, and azelnidipine. TNF-induced phosphorylation of ERK and Akt, but not p38 MAPK, was attenuated by nicardipine, cilnidipine, benidipine, efonidipine, and azelnidipine. By contrast, GM-CSF-induced phosphorylation of ERK, p38 MAPK, and Akt was affected by neither blockers. GM-CSF-induced neutrophil migration was also suppressed by amlodipine and nicardipine, but not by azelnidipine, when these blockers were assessed for their effect on neutrophil migration. These findings suggest that some calcium channel blockers can suppress cytokine-induced neutrophil activation, leading to possible prevention of the progression of atherosclerosis, and that activation of the ERK and PI3K/Akt pathways induced by TNF, but not by GM-CSF, is selectively affected by some blockers. [J Physiol Sci. 2008;58 Suppl:S74]
