Nifedipine increases cholesteryl ester hydrolytic activity in lipid-laden rabbit arterial smooth muscle cells. A possible mechanism for its antiatherogenic effect.
Calcium and cholesterol (CHOL) accumulation are characteristic features of human atherosclerotic plaques. Calcium channel blockers have been shown to increase calcium levels in myocardial cells and suppress free and esterified CHOL deposition in arteries of CHOL-fed animals. To test the hypothesis that Nifedipine alters CHOL metabolism, thereby decreasing free and esterified CHOL accumulation in smooth muscle cells (SMC), we cultured arterial SMC from rabbits fed a normal or egg-supplemented diet for 6 mo. Cultured cells were treated with 0.1 mg/liter Nifedipine every 3 d during a 1-wk experiment. Although Nifedipine significantly increased lysosomal and cytoplasmic cholesteryl ester (CE) hydrolase activity in normal SMC via increased levels of intracellular cyclic AMP, no change in total CHOL content was observed after 1 wk of Nifedipine treatment. Contrary to these observations, lipid-laden SMC demonstrated a significant 50% loss in CHOL and CE after treatment with Nifedipine, due in part to the observed increase in CE hydrolytic activities. These data support our hypothesis that Nifedipine decreases CHOL and CE accumulation in arterial SMC by increasing arterial CE hydrolysis.
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy*; D002417:Cattle; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005260:Female; D008247:Lysosomes / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D011817:Rabbits; D002787:Sterol Esterase / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D002784:Cholesterol; D002787:Sterol Esterase; D001616:beta-Galactosidase; D009543:Nifedipine