The effect of nifedipine on lipid and monocyte infiltration of the subendothelial space.
OBJECTIVE
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 subendothelial space, an endothelial cell (EC)-smooth muscle cell (SMC) bilayer model of the arterial wall was incubated for 18 hours with nifedipine (0.1 micrograms/ml). Iodine 125-labeled low-density lipoprotein (125I-LDL) (10 micrograms 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 125I-LDL in a concentration-dependent fashion, without saturation to 25 micrograms/ml, the highest concentration studied. Nifedipine increased monocyte uptake of LDL (10 micrograms/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.
Alexander
J J
JJ
Department of Surgery, Case Western Reserve University, Cleveland Metropolitan General Hospital, OH 44109.
Miguel
R
R
Piotrowski
J J
JJ
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D002118:Calcium / Q000502:physiology; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009543:Nifedipine / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D009543:Nifedipine; D002118:Calcium