Inhibition of lipid deposition in the hypercholesterolemic rat by clentiazem, a calcium channel blocker.
We studied the effects of clentiazem, a calcium channel blocker (1) on the accumulation of lipid in the aorta, (2) on the level of plasma lipids, and (3) on the number of adherent intimal monocytes and foam cells. Seventy Wistar rats were assigned to one of the following groups: (1) regular diet, (2) an atherogenic diet consisting of regular chow with 2% cholesterol, 1% cholic acid, and 0.5% thiouracil (CCT), (3) CCT supplemented with 5 mg/kg/day clentiazem, and (4) CCT with 25 mg/kg/day clentiazem. Animals were sacrificed after 6 or 12 weeks of diet. Aortas were studied by light microscopy after staining with oil red O (ORO) and/or hematoxylin. ORO staining was quantified in both abdominal and thoracic regions of the aorta. The aortas of the clentiazem groups demonstrated significantly less ORO staining than CCT diet controls in thoracic aorta after 6 weeks and abdominal aorta after 12 weeks. There was no significant difference in the plasma lipid concentrations. The clentiazem-treated groups had fewer numbers of adherent monocytes and foam cells. We conclude that clentiazem inhibits lipid deposition in cholesterol-fed rats without lowering plasma lipid concentrations and that the number of intimal monocytes and foam cells is decreased in the presence of this calcium antagonist.
Nunnari
J J
JJ
Department of Pathology, University of Massachusetts Medical School, Worcester 01655.
Fisher
M
M
White
S D
SD
D000818:Animals; D001011:Aorta / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology*; D002448:Cell Adhesion / Q000502:physiology; D002452:Cell Count; D002784:Cholesterol / Q000494:pharmacology; D002793:Cholic Acids / Q000494:pharmacology; D004036:Diet, Atherogenic; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006339:Heart Rate / Q000502:physiology; D006937:Hypercholesterolemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis / Q000097:blood; D008297:Male; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013889:Thiouracil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002793:Cholic Acids; D008055:Lipids; C056595:clentiazem; D013889:Thiouracil; D002784:Cholesterol; D004110:Diltiazem