THE EFFECT OF NIFEDIPINE ON LIPID AND MONOCYTE INFILTRATION OF THE SUBENDOTHELIAL SPACE

Purpose: Calcium channel blockade has been shown to inhibit experimental atherosclerosis in cholesterol-fed animals, and early clinical trials suggest its benefit in human subjects as well. Methods: To determine the effect of the calcium channel blocker nifedipine on lipid and monocyte infiltration of the subendothetial space, an endothelial cell (EC)-smooth muscle cell (SMC) bilayer model of the arterial wall was incubated for 18 hours with nifedipine (0.1 mug/ml). Iodine 125-labeled low-density lipoprotein (I-125-LDL) (10 mug protein/ml) was then added to the upper-well medium. Results. After a 3-hour incubation period, nifedipine-treated bilayers showed an increased permeability to LDL (p < 10(-7)). Nifedipine had no effect on the membrane binding or cellular uptake of LDL by the EC but did increase SMC binding and uptake (p < 0.0005). U937 monocytes were found to incorporate I-125-LDL in a concentration-dependent fashion, without saturation to 25 mug/nil, the highest concentration studied. Nifedipine increased monocyte uptake of LDL (10 mug/ml; p < 0.003 but reduced monocyte movement through the EC barrier (p < 10(-7)). A study of the selective preincubation of each cell type (EC, SMC, and monocyte) with nifedipine indicated that this reduction was likely the result of a direct effect on the monocyte. Conclusions: Given the potential cytotoxic effects of the monocyte within the subendothelial space, nifedipine-induced inhibition of monocyte infiltration and enhancement of lipoprotein uptake by the SMC may be protective.