Low density lipoprotein-lowering and high density lipoprotein-elevating effects of nicardipine in rats.
Oral administration of a calcium antagonist, nicardipine hydrochloride (simply designated as nicardipine), in doses of 10-100 mg/kg tended to decrease total serum cholesterol and to increase high density lipoprotein (HDL) cholesterol in the normal rat. These effects of nicardipine were much greater than those of clofibrate, a standard cholesterol-lowering drug. Neither nicardipine nor clofibrate caused significant alteration in serum triglyceride and phospholipid. In hypercholesterolemic rats, nicardipine increased significantly HDL cholesterol with a reduction of total serum cholesterol, whereas clofibrate did not change HDL cholesterol. Separation of serum lipoproteins either by ultracentrifugation in various densities of KBr-NaCl solution or by polyacrylamide gel electrophoresis demonstrated that nicardipine increased preferentially HDL2 (density: 1.063-1.125), with a reduction of the low density lipoprotein (LDL) (density: 1.006-1.063) level in hypercholesterolemic rats. Serum triglyceride and liver phospholipid were increased slightly by nicardipine with no clear dose-dependency. Clofibrate also increased serum triglyceride. In normal rats, neither nicardipine nor nicotinic acid inhibited sterol biosynthesis from [1-14C]acetate in the liver, whereas clofibrate inhibited sterol production. Oral administration of [4-14C]cholesterol to hypercholesterolemic rats indicated that nicardipine had no inhibitory effect on the intestinal absorption of cholesterol.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D002994:Clofibrate / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013261:Sterols / Q000096:biosynthesis
D000085:Acetates; D000960:Hypolipidemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D013261:Sterols; D002784:Cholesterol; D009529:Nicardipine; D002994:Clofibrate; D009543:Nifedipine