Suppression of atherogenesis in cholesterol-fed rabbits treated with nilvadipine, a new vasoselective calcium entry blocker.
We examined the effects of nilvadipine, a new dihydropyridine calcium entry blocker, on atherogenesis in rabbits fed a 1% cholesterol diet. The drug was given subcutaneously to the animals in hypotensive doses of 1.0 or 3.2 mg/kg/day for 10 weeks, and was well tolerated. Plasma total cholesterol increased markedly in all the cholesterol-fed rabbits, and nilvadipine had no effect on this, or on HDL-cholesterol and triglyceride levels. However, the area of Sudan IV positive intimal lesions (one of the parameters of atherosclerosis) in the aorta decreased significantly in the nilvadipine treated animals, and in addition, cholesterol and calcium content in the thoracic aorta were reduced. The reference drugs, nifedipine and nicardipine given subcutaneously in doses of 10.0 mg/kg/day either had no effect or were weaker in antiatherogenic effect than nilvadipine. The findings suggest that nilvadipine has more potent antiatherogenic activity than nicardipine or nifedipine.
Koibuchi
Y
Y
Product Development Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sakai
S
S
Miura
S
S
Ono
T
T
Shibayama
F
F
Ohtsuka
M
M
D000818:Animals; D001013:Aorta, Thoracic / Q000032:analysis; D001161:Arteriosclerosis / Q000517:prevention & control*; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002784:Cholesterol / Q000032:analysis; D008099:Liver / Q000032:analysis; D008297:Male; D009206:Myocardium / Q000032:analysis; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits
D002121:Calcium Channel Blockers; C035100:nilvadipine; D002784:Cholesterol; D009529:Nicardipine; D009543:Nifedipine; D002118:Calcium