The effects of diltiazem, a calcium antagonist, on the development of atherosclerosis were studied in Japanese white rabbits. The rabbits were examined at the end of 10 weeks on the following regimens; 1) a diet of standard pellets and daily intraperitoneal (ip) injections of saline; 2) a diet of pellets containing 1 % cholesterol and daily ip injections of saline; or 3) a diet of pellets containing 1% cholesterol and daily ip injections of diltiazem (50 mg). The plasma total and LDL cholesterol levels for the third group were significantly lower than those of the cholesterol diet group. Macroscopically, atheromatous lesions covered 26.7% ± 6.7% (mean ± SE) of the intimal surface of the aorta in the second group, and 0.7% ± 0.3% in the third group (p < 0.005). The levels of cholesterol, calcium, and uronic acid in the aortic tissue of the second group were significantly higher than those in the third. We concluded that diltiazem administered intraperitoneally suppresses the plasma total and LDL cholesterol elevation induced by the cholesterol diet and inhibits experimentally-induced atherosclerosis. (Arteriosclerosis 6:237-241, March/April 1986) R ecently, C a + + antagonists, which appear to act by inhibiting transmembranous C a + + flux and/or the release and binding of intracellular Ca + + , 1 " 5 have been reported to suppress experimentally induced atherosclerosis.6 " 9 On the other hand, a few studies have demonstrated that nifedipine and diltiazem, given orally, have no antiatherosclerotic effect.10 " 12 Ca + + antagonists are widely used to treat ischemic heart diseases, spastic angina, and hypertension. In this study we examined the effects of intraperitoneally administered diltiazem on plasma total cholesterol and cholesterol desposition in the aorta of rabbits given a 1 % cholesterol diet.
Methods AnimalsTwenty male Japanese white rabbits, each weighing about 2.0 kg, were housed individually under controlled conditions and divided into three groups; 1) a standard diet group (n = 7) given 100 g of standard rabbit pellets (Clea Japan Incorporated), and receiving daily intraperitoneal (ip) injections of saline; 2) a cholesterol diet group (n = 8)From the 2nd Department of Internal Medicine and the Department of Pathology and Surgical Pathology, University of Occupational and Environmental Health Japan, School of Medicine, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, Japan.Address for reprints: Dr. Yasuhide Nakashima, The 2nd Department of Internal Medicine, University of Occupational and Environmental Health Japan, 1-1, Iseigaoka, Yahatanishiku, Kitakyushu, 807, Japan.Received May 22,1985; revision accepted November 25,1985. fed pellets containing 1% cholesterol, and injected (ip) with saline; and 3) a diltiazem-treated group (n = 5) fed pellets containing 1% cholesterol and receiving daily ip injections of diltiazem (50 mg). Water was given ad libitum. After 10 weeks on these regimens, the rabbits were injected with 2 ml of a 5% pentobarbital solution and killed by bleeding from a femoral artery. Dilti...