Inhibitory effect of clentiazem (TA-3090), a new calcium antagonist, on balloon catheter-induced intimal thickening of rabbit aorta.
Male Japanese white rabbits were fed a restricted amount (100 g/head/day) of an atherogenic diet containing 0.2% cholesterol and 6% peanut oil during an 8-week experimental period. Atherosclerotic lesions, characterized by intimal thickening with lipid deposition, were produced by de-endothelialization of the rabbit aorta with a 4 F balloon catheter halfway through the experiment. Clentiazem (TA-3090), a new calcium antagonist, was administered at an oral dose of 30 mg/kg/day for 4 weeks starting on the day of deendothelialization. Clentiazem significantly depressed the intimal thickening without any effect on serum lipid levels. Clentiazem (1, 3, and 10 microM) significantly and dose-dependently inhibited the in vitro proliferation of smooth muscle cells that had been explanted from the neointima of the deendothelialized aorta. At a higher concentration, this drug markedly inhibited collagen-induced aggregation of rabbit platelets. Diltiazem also showed similar effects, but the effects of clentiazem were more potent than those of diltiazem. These results suggest that clentiazem exhibits an antiatherogenic effect, at least partly through prevention of smooth muscle cell proliferation in atheromatous lesions, in addition to its hypotensive action.
Saso
Y
Y
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Ohtani
A
A
Odawara
A
A
Iwasaki
H
H
Takashima
K
K
Morita
T
T
D000818:Animals; D001018:Aortic Diseases / Q000473:pathology / Q000517:prevention & control*; D001161:Arteriosclerosis / Q000473:pathology / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002404:Catheterization; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000097:blood; D004036:Diet, Atherogenic; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D008055:Lipids / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011817:Rabbits
D002121:Calcium Channel Blockers; D008055:Lipids; D010975:Platelet Aggregation Inhibitors; C056595:clentiazem; D003094:Collagen; D004110:Diltiazem