METABOLISM OF CHOLESTEROL ESTERS IN CULTURED MACROPHAGES UNDER THE ACTION OF THE CALCIUM-CHANNEL BLOCKERS VERAPAMIL AND NIFEDIPINE

The influence of verapamil and nifedipine on the following parameters of the metabolism of cholesterol esters (ChE) was studied in a culture of mouse macrophages: 1) incorporation of [C-14]oleate into ChE; 2) content of total and free cholesterol (FCh); 3) release of [C-14]oleate from ChE and incorporation of [H-3]FCh into ChE; 4) excretion of [H-3]FCh from cells. Verapamil and nifedipine (10-100-mu-M) produced a dose-dependent decrease in the incorporation of [C-14]oleate into ChE and increased the content of FCh without affecting the content of total Ch in the cells during the culturing of macrophages in the presence of acetylated low-density lipoproteins. Both these compounds stimulated the incorporation of [H-3]FCh into the cell ChE. Verapamil and nifedipine in pharmacological concentrations (25-75-mu-M) increased the excretion of [H-3]FCh from macrophages into the culture medium containing high-density lipoproteins and 20% embryonic serum. The results obtained are evidence that the antiatherogenic action of verapamil and nifedipine is exerted through a decrease in the intracellular synthesis of ChE and an increase in the rate of hydrolysis of ChE and excretion of Ch from the cells.