Inhibition of cholesteryl ester deposition in macrophages by calcium entry blockers: an effect dissociable from calcium entry blockade

The effects of calcium entry blockers on stimulated cholesteryl [³H]‐oleate deposition in cultured macrophages were characterized in order to elucidate mechanisms underlying possible antiatheros‐clerotic effects. Stimulation of intracellular cholesteryl [³H]‐oleate deposition was initiated by incubation of macrophages with β‐very low density lipoproteins (β‐VLDL). Nifedipine (Class I) markedly reduced cholesteryl [³H]‐oleate deposition at all concentrations tested. However, Bay K 8644, a dihydropyridine which is known to stimulate calcium entry, also reduced cholesteryl [³H]‐oleate deposition with a similar potency to nifedipine. The effects of three Class II calcium entry blockers were evaluated: verapamil, methoxyverapamil, and diltiazem. Verapamil inhibited cholesteryl [³H]‐oleate deposition in a concentration‐dependent manner. Similarly, methoxyverapamil reduced cholesteryl [³H]‐oleate deposition in a concentration‐dependent manner although the reduction was not as great as that produced by verapamil. In contrast, diltiazem at any concentration tested did not inhibit cholesteryl [³H]‐oleate deposition. Flunarizine (a Class III calcium entry blocker) produced a modest stimulation of cholesteryl [³H]‐oleate deposition at the lowest concentration used (10⁻⁷ m) but marked depression at the highest concentration (10⁻⁵ m). The results indicate calcium entry blockers may exert protective effects on the development of atherosclerosis in animal models of diet‐induced hyperlipidaemia by inhibiting intracellular cholesteryl ester deposition, but this effect may not be related to their calcium entry‐blocking effects. 1987 British Pharmacological Society