Protective action of a calcium antagonist, nilvadipine, against aortic calcium deposition--a pathogenic factor in atherosclerosis

Nilvadipine and other calcium antagonists were studied for their effect on 1-alpha-hydroxyvitamin D3 (1 - alpha (OH)D3)-induced aortic calcium deposition in rats. The animals were treated orally with 1-alpha (OH)D3 (10 micrograms/kg) for 2 weeks. Calcium antagonists were given orally twice a day during the same period. The aortic calcium content in 1-alpha (OH)D3-treated rats increased to about 100 times that in the control. Nilvadipine reduced the aortic calcium deposition dose-dependently, with percent inhibition of 6, 43, 72 and 92%, at doses of 0.1, 1, 10 and 100 mg/kg, respectively. Similar activities were obtained for the other calcium antagonists except diltiazem which had no effect even at the largest dose of 100 mg/kg. According to the ED50 values, nilvadipine (2.2 mg/kg) was more potent than nifedipine (23.2 mg/kg), nicardipine (12.4 mg/kg) and verapamil (32.0 mg/kg). Scanning and transmission electron microscopy showed clear-cut degenerative changes in the endothelial cells after 1-alpha (OH)D3 treatment. Nilvadipine exerted a protective effect against these degenerative changes but not against 1-alpha (OH)D3-induced hypercalcemia. Furthermore, the drug had only minimal effect on in vitro calcification of the aorta. Our findings suggest that nilvadipine inhibits aortic calcification by protecting the aortic wall cells.     

Effects of anticalcifying and antifibrobrotic drugs on pre-established atherosclerosis in the rabbit.

The effects of the anticalcifying drug, ethane-hydroxydiphosphonate (EHDP) and the inhibitors of collagen biosynthesis, colchicine, penicillamine and azetidine were studied in the rabbit with pre-established atherosclerosis. The drugs were administered with a cholesterol-free diet (regression diet) for 8 weeks following the induction of atherosclerosis by feeding a hypercholesterolemic diet containing 2% cholesterol and 8% peanut oil for 8 weeks. The extent and severity of aortic atherosclerosis, as revealed by the morphological and biochemical findings, increased significantly during the regression period. In rabbits treated with EHDP (5 mg/kg/day) the aorta had fewer gross lesions and contained significantly less cholesterol, collagen and elastin than did the aorta of the rabbits fed the regression diet alone. These changes were associated with a significant reduction in aortic calcium caused by EHDP. The aortic content of cholesterol, collagen and elastin in the EHDP-treated rabbits, although less than that of the rabbits fed the regression diet alone, was about the same as that of the rabbits fed a high cholesterol diet for 8 weeks. Both colchicine (0.2 mg/kg/day) and penicillamine (100 mg/kg/day) had a selective action on the induced plaques in that they suppressed the fibrous proliferation in the lesions without preventing lipid and calcium accumulation in the lesions. Neither colchicine nor penicillamine reduced the extent of aortic atherosclerosis as determined by gross examination of the vessel. Azetidine had no significant effect on the pre-established atherosclerotic lesions. The lipid, fibrous protein and calcium content of the aorta of the azetidine-treated animals was not significantly different from that of the untreated animals. The biochemical findings in the aorta were consistent with the microscopic changes.     

硝苯吡啶,硫氮zuo酮和赤芍对家兔动脉粥样硬化形成的影响

The effects of nifedipine, diltiazem, and Paeonia lactiflora Pall (PLP) on serum lipids. Plasma lipid peroxides (LPO), TXB2, and 6-keto-PGF1 alpha in cholesterol-fed rabbits have been investigated. Oral administration of nifedipine (15 mg/kg.d), diltiazem (30 mg/kg.d), and PLP (5 g/kg.d) caused 60.8%, 45.2%, and 74.2% reduction in the area of atherosclerosis in the aorta respectively. The levels of plasma LPO and TXB2 and the contents of cholesterol, phospholipid, and calcium in the intimal-media of the aorta in the treated groups were significantly lower than those in the cholesterol group, but the level of plasma 6-keto-PGF1 alpha in the treated groups was significantly higher. The appearance of cholesterol-induced TXB2 elevation and 6-keto-PGF1 alpha decrease in the treated groups was delayed. There are positive correlation between plasma TXB2 and the followings: serum lipids, plasma LPO, and the content of calcium in the intimal-media of the aorta, and the percentage of area of lesion in the aorta, while plasma 6-keto-PGF1 alpha showed significantly negative correlation with the above data. TXB2/6-keto-PGF1 alpha was found to be positively correlated with the percentage of lesion area of the aorta. It was shown that Ca2+ metabolism plays an important role in thromboxane, prostaglandin, and LPO metabolism. In conclusion, the inhibition of LPO production and regulation of TXA2-PGI2 balance may be one of the main mechanisms of the antiatherogenic effects of calcium antagonists and PLP.     

Failure of nifedipine to reduce atherogenesis in cholesterol-fed rabbits

The purpose of this study was to determine if therapeutic dosages of nifedipine, a drug that reduces intracellular calcium concentrations, suppresses atherogenesis in normotensive, cholesterol-fed rabbits. Control groups were fed either normal chow (Group I), or normal chow supplemented with 0.10 and 0.25% cholesterol (wt/wt) (Group II). Group III animals were fed the same diets as Group II animals and received nifedipine (0.625 and 1.250 mg/kg/d). During the course of the study (3 months) no systematic quantitative difference (P greater than 0.05) was observed between Groups II and III with regard to mean arterial blood pressure, serum cholesterol, serum electrolytes (sodium and potassium), plasma renin activity, or serum lipoprotein classes. At necropsy, there likewise was no difference in affected aortic surface area, aortic cholesterol content, or renal renin content. We conclude that nifedipine, at human therapeutic dosages, has no effect on either atherogenesis or the renin-angiotensin system in normotensive rabbits fed a moderately cholesterol-rich diet.     

Effects of nilvadipine,a calcium antagonist,on intimal thickness of vascular grafting in cholesterol-fed rabbits

The effects of nilvadipine on intimal thickness in expanded poly-tetrafluoroethylene grafts were examined in 21 rabbits undergoing infrarenal aorta reconstruction. Seven rabbits received commercial rabbit chow (control group), seven, a regular diet supplemented with 1% cholesterol (cholesterol group); and seven, the cholesterol diet with 98.9% pure nilvadipine 1 mg/kg/day (nilvadipine group). Grafts were harvested 3 months after surgery for histologic examination. Intimal thickness at the proximal and distal anastomosis was, respectively, 225±76 and 273±110 m in the control group, 525±236 and 600±250 m in the cholesterol group, and 284±94 and 241±86 m in the nilvadipine group. Intimal thickness in the cholesterol group was significantly greater than in the nilvadipine group (p<0.01). The smooth muscle cell values in the intima at the proximal and distal anastomosis were, respectively, 10.6±3.6 and 12.6±3.2 %Extinction (%E) in the control group, 15.5±4.0 and 16.1±4.5 %E in the cholesterol group, and 9.1±3.1 and 9.6±2.1 %E in the nilvadipine group. The smooth muscle cell value in the intima of the cholesterol group was greater than that of the nilvadipine group (p<0.01). These data suggest that nilvadipine significantly reduces the degree of intimal thickness in expanded polytetrafluoroethylene grafts in cholesterol-fed rabbits, and that this effect is due to inhibition of smooth muscle cell migration and proliferation.     

The antiatherogenic dose response effect of verapamil in an experimental atherosclerosis model in the rabbit.

The aim of the study was to assess the dose dependence of the antiatherogenic effect of verapamil (Isoptin, Lek Ljubljana, Yugoslavia) in rabbits fed 1% cholesterol diet. Verapamil was administered subcutaneously at doses of 0.25, 1 and 2 mg.kg-1/day at 12-hour intervals for 8 weeks. The results indicate verapamil administered s.c. exerts a preventive anti-atherosclerotic effect only in therapeutic doses (0.25 mg.kg-1). The beneficial effect of low-dose verapamil can also be seen in the spectrum of serum lipids as the drug lowers the levels of total cholesterol and triacylglycerols. Compared with the results obtained from a group receiving diet without Ca-antagonist premedication, high doses do not reduce the extent of atheromatous plaques.     

Nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in Watanabe heritable hyperlipidemic rabbits

We studied the effects of nifedipine, a calcium antagonist, on atherosclerosis in cholesterol-fed rabbits and Watanabe heritable hyperlipidemic rabbits (WHHL rabbits). Japanese White rabbits were fed 120g of 2% cholesterol rabbit chow daily, and WHHL rabbits were fed standard rabbit chow. In each experiment, the rabbits were divided into two groups. Twenty milligrams of nifedipine was given orally twice a day to the nifedipine group, and the control group was given a placebo in the same way. The rabbits were sacrificed at the end of the 12th week in the case of cholesterol-fed rabbits, and the 20th week in the case of WHHL rabbits. Among the cholesterol-fed rabbits, the percentage of aortic intimal surface area covered by atherosclerotic lesions (AS%) was 25.9 +/- 7.6% (mean +/- S.D.) in the nifedipine group (n = 7), and 55.6 +/- 22.8% in the placebo group (n = 8) (p less than 0.01). The cholesterol content of thoracic and abdominal aorta in the nifedipine group was lower than those in the placebo group (p less than 0.05). Among the WHHL rabbits, the AS% was 33.4 +/- 14.1% in the nifedipine group (n = 5), and 27.0 +/- 11.7% in the placebo group (n =6) (n.s.). The aortic cholesterol and calcium contents also showed no significant differences between the two groups. We concluded that nifedipine suppressed atherosclerosis in cholesterol-fed rabbits but not in WHHL rabbits. The different responses suggest that the effect of nifedipine could be mediated by low density lipoprotein receptors or that the early exposure to hyperlipidemic serum from birth might affect cell functions of WHHL rabbits.     

Nifedipine reduces atherogenesis in cholesterol-fed heterozygous WHHL rabbits

We have developed a new model to study the interaction between diet and genetics in atherogenesis, the cholesterol-fed heterozygous WHHL rabbit. To determine the effects of calcium blockers on atherosclerosis in this model, two groups of heterozygous WHHL rabbits were fed 0.25% cholesterol and 2% peanut oil with (n = 6) and without (n = 6) oral nifedipine (40 mg/kg/day) for 16 weeks. Body weights, serum cholesterol, triglycerides and calcium, and blood pressures were not significantly different between the 2 groups during the study period. Heterozygous WHHL rabbits in the nifedipine group had less aortic surface area with sudanophilic lesions (23 +/- 15% vs. 62 +/- 18%, P less than 0.01) and fewer segments of coronary arteries with lesions (19 +/- 9% vs. 35 +/- 8%, P less than 0.02). Total aortic cholesterol, phospholipid, and calcium were also reduced in nifedipine-treated rabbits compared with untreated animals. We conclude that nifedipine reduced atherosclerosis in this model. Although the mechanism is unknown, it is apparent that nifedipine acts independently of changes in plasma lipids and blood pressure.     

Low-dose cerivastatin inhibits spontaneous atherogenesis in heterozygous watanabe hyper lipidemic rabbits

The aim of this study was to investigate whether cerivastatin (BAYw6228), a new potent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, was able to prevent atherogenesis in heterozygous Watanabe heritable-hyperlipidemic (WHHL) rabbits, a model never tested before using this HMG-CoA reductase inhibitor. The heterozygous WHHL rabbits of our breeding developed mild hypercholesterolemia along with focal atherosclerotic lesions in the thoracic aorta. A 9-week treatment with cerivastatin at doses comparable to those used in humans (50 microg/kg/day) reduced serum total cholesterol levels (from 94.4 +/- 10.9 to 43.6 +/- 10.5 mg/dl, p < 0.005) and prevented aortic lesion development (intima/media ratio: 0.058 +/- 0.032 vs 0.946 +/- 0.282 in the placebo group, p < 0.0005). Using a panel of monoclonal antibodies specific to macrophages and able to recognize different smooth muscle cell (SMC) phenotypes, we observed that cerivastatin treatment affected the differentiation properties of SMCs and drastically reduced SMC and macrophage accumulation in the intima of the thoracic aorta. These data show that in the presence of moderate atherosclerotic lesions, such as those of heterozygous WHHL rabbits, low doses of cerivastatin exert an antiatherogenic effect.     

Effects of reserpine on expression of the LDL receptor in liver and on plasma and tissue lipids, low density lipoprotein and fibrinogen in rabbits in vivo

The effects of administering reserpine (0.1 mg/kg) or 17alpha-ethinyloestradiol (2.5 mg/kg) to New Zealand White rabbits on low density lipoprotein receptors in liver, on plasma low density lipoprotein and fibrinogen and on plasma and tissue lipids were determined. Blood pressure and heart rate were also followed. The drugs were injected subcutaneously into conscious unrestrained rabbits for 5 days. On the 6th day homologous 125I-tyramine cellobiose labelled low density lipoprotein (125I-TC-LDL) was injected intravenously and 24 h later the animals were killed. Compared to controls, reserpine significantly increased LDL receptor expression in the liver by about threefold, and reduced total cholesterol in plasma, aorta and heart, without affecting plasma triglycerides. The reductions in plasma cholesterol and heart were due to decreases in both unesterified and esterified cholesterol. Similar effects were observed with oestrogen, except that there was no change in esterified cholesterol in aorta. In liver, a decrease of 24% in total cholesterol was due mainly to decreased esterified cholesterol. In adrenal glands total cholesterol increased by 25%. Reserpine significantly accelerated the plasma clearance of intravenously injected homologous 125I-TC-LDL and reduced its accumulation in aortic wall. Neither reserpine nor oestradiol affected blood pressure, haematocrit or plasma fibrinogen. The results suggest that reserpine is an affective anti-atherogenic drug capable of decreasing cholesterol in plasma, arteries and heart by increasing high affinity LDL receptors in the liver.     

Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery

The antiatherogenic activity of FR34235 (Nilvadipine), a calcium antagonist, was examined in rabbits with carotid arteries sheathed with polyethylene cuffs, and compared with that of nifedipine, verapamil and diltiazem. The drugs were given intramuscularly in daily doses of 0.01-10 mg/kg for 3 weeks, starting on the day of cuff-placement. FR34235 dose-dependently inhibited the cuff-induced intimal thickening, and was more potent than the other calcium antagonists, whose order of potency was nifedipine, diltiazem and verapamil. In an in vitro experiment on inhibition of migration of rat aortic smooth muscle cells, using zymosan-activated air pouch exudate as a chemoattractant in modified Boyden chambers, FR34235 was also the most potent among the calcium antagonists tested. The IC50 values were 3.3 X 10(-11) M for FR34235, 1.7 X 10(-10) M for nifedipine, 6.0 X 10(-9) M for verapamil and 2.4 X 10(-7) M for diltiazem. Effects of these drugs on proliferation of rat aortic smooth muscle cells and rabbit platelet aggregation were also examined in vitro. At concentrations less than 10(-5) M, none of the drugs inhibited proliferation of the smooth muscle cells, and only verapamil inhibited collagen-induced platelet aggregation (IC50 = 9.0 X 10(-7) M). It is suggested that FR34235 should be useful for preventing and treating atherosclerosis. Inhibition of smooth muscle cell migration is thought to be its mechanism of antiatherogenic activity.     

Effect of verapamil on accumulation of free and esterified cholesterol in the thoracic aorta of cholesterol-fed rabbits

In order to investigate the effect of the calcium antagonist verapamil on atherogenesis in cholesterol-fed rabbits, 3 groups of 11 animals were fed a 2% cholesterol-enriched diet for 10 weeks. One group received verapamil in a daily dose of 16 mg/kg orally plus 2 mg/kg subcutaneously. This dosage resulted in plasma concentrations of verapamil in the same range as the usual therapeutic levels in humans. Another group received verapamil in a daily dose of 8 mg/kg orally and 0.5 mg/kg subcutaneously. The third group received placebo capsules orally and isotonic saline subcutaneously. Total cholesterol concentrations in plasma over the 10 weeks were 37 +/- 4, 42 +/- 4 and 45 +/- 3 mM (mean +/- SE) in the high verapamil-, in the low verapamil- and in the placebo group, respectively. These values were not significantly different. The distribution of cholesterol between HDL, LDL and VLDL in plasma was similar in the 3 groups. The high verapamil group had a significantly (P less than 0.05) lower concentration of cholesterol in the thoracic aorta than the placebo group (29 +/- 5 vs 43 +/- 9 mumol/g wet weight). The low verapamil group and the placebo group had the same aortic cholesterol concentrations. Neither dosage of verapamil affected the permeability of the aortic endothelium to plasma lipoproteins and albumin, as measured by use of radioactive tracers at the end of the experiment.     

A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits

BACKGROUND: The remarkable anti-atherosclerotic effects of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor have not been demonstrated in diet induced severe hyperlipidemia in rabbit model. OBJECTIVE: We have investigated the effect of pitavastatin, a newly developed statin, on atherosclerosis in rabbits. METHODS AND RESULTS: Oophorectomized female NZW rabbits were fed 0.3% cholesterol chow for 12 weeks with or without pitavastatin (0.1mg/kg per day) (Gp.NK and HCD). The level of serum cholesterol was decreased in Gp.NK compared with Gp.HCD (772.8 +/- 70.2 versus 1056.9 +/- 108.3 mg/d), whereas no significant alterations were observed in triglyceride and HDL-cholesterol. NO dependent response stimulated by acetylcholine and calcium ionophore A23187 and tone related basal NO response induced by N(G)-monomethyl-l-arginine acetate were all improved by pitavastatin treatment. Pitavastatin treatment increased the level of cyclic GMP in the aorta of cholesterol fed rabbits. In the aorta, the expression of eNOS mRNA was significantly up regulated and O(2)(-) production was slightly reduced in Gp.NK animals. Atherosclerotic area was significantly decreased in aortic arch and thoracic aorta from Gp.NK compared with those from Gp.HCD ( 15.1 +/- 5.3 versus 41.9 +/- 10.2%, 3.1 +/- 1.1versus 7.9 +/- 1.2% in Gp.NK and Gp.HCD aortic arch and thoracic aorta). Anti-macrophage staining area, the MMP1 or 2 and the nitrotyrosine positive area were decreased in Gp.NK. CONCLUSION: Pitavastatin retards the progression of atherosclerosis formation and it improves NO bioavailability by eNOS up-regulation and decrease of O(2)(-).     

Inhibitory effect of clentiazem (TA-3090), a new calcium antagonist,on balloon catheter-induced intimal thickening of rabbit aorta

Summary 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 µM) 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.     

绞股蓝总皂甙对兔实验性动脉粥样硬化斑块形成的影响

为了探讨绞股蓝总皂甙防止动脉粥样硬化的作用及其机制，在新西兰兔食饵性动脉粥样硬化模型上观察了绞股蓝总皂甙治疗性给药对主动脉壁粥样硬化斑块形成及脂质过氧化的影响。发同绞股蓝总皂甙（１２０ｍｇ／ｄ）治疗四周能减少主动脉壁块形成，苏丹Ⅳ当色及形态计量学分析显示绞股蓝总皂甙治疗组的斑块面积较之高脂组减少了３７％；主动脉壁脂质过氧化程度也明显减轻，丙二醛含量仅为高脂组的６７％。此外，还观察到绞股蓝总皂甙在减     

绞股蓝总皂甙对兔实验性动脉粥样硬化斑块形成的影响

为了探讨绞股蓝总皂甙防止动脉粥样硬化的作用及其机制．在新西兰兔食饵性动脉粥样硬化模型上，观察了绞股蓝总皂甙治疗性给药对主动脉壁粥样硬化斑块形成及脂质过氧化的影响。发现绞股蓝总皂甙（120mg／d）治疗四周能减少主动脉壁斑块形成．苏丹IV染色及形态计量学分析显示绞股蓝总皂甙治疗组的斑块面积较之高脂组减少了37％；主动脉壁脂质过氧化程度也明显减轻，丙二醛含量仅为高脂组的67％。此外，还观察到绞股蓝总皂甙在减少主动脉壁斑块形成和脂质过氧化的同时，还能保护血管壁释放或合成一氧化氮的能力，并防止因长期高胆固醇血症引起的主动脉壁Ca2 超载。绞股蓝总皂甙的作用与抗氧化剂维生素E相似。     

A randomized double-blind crossover study of nicardipine and nifedipine in patients with angina pectoris and concomitant essential hypertension

Summary The two dihydropyridine calcium antagonists, nicardipine and nifedipine, were compared in 12 patients with both stable angina pectoris and systemic hypertension using a double-blind, crossover protocol. After a 2-week placebo run-in period, each patient was randomized to either nicardipine or nifedipine; each drug was titrated up to either blood pressure normalization, appearance of adverse effects, or maximal dosage (40 mg, three times a day with nicardipine and 30 mg, three times a day with nifedipine) and then administered for 4 weeks. Maximal symptom-limited exercise tests were performed at the end of the placebo run-in and each treatment period, 3 and 8 hours after drug administration. Nicardipine and nifedipine were used at the mean doses of 100±20 mg/day and 57±20 mg/day, respectively. Both drugs reduced, significantly and similarly, standing and supine blood pressure, frequency of anginal episodes, and nitroglycerin consumption. At 3 hours after drug administration, exercise duration and time to 1-mm ST depression increased significantly from 402±84 and 306±108 seconds, respectively, with placebo; to 533±135 and 442±138 seconds during nicardipine; and to 518±118 and 437±133 seconds during nifedipine, with a concomitant reduction of peak ST depression. Both submaximal and maximal exercise diastolic blood pressure were significantly reduced by the two calcium antagonists whereas systolic blood pressure was decreased only at submaximal but not at maximal exercise; the heart rate was not significantly modified by the two drugs at any exercise stage. The rate-pressure product decreased from 169±17 to 151±25 with nicardipine and 152±24 with nifedipine at submaximal exercise, but was not significantly modified at the onset of 1-mm ST depression and maximal exercise. Thus, nicardipine and nifedipine showed a similar hypotensive and antianginal activity; the only important difference between the two drugs emerged from the exercise tests performed 8 hours after drug administration; although nifedipine still maintained a slight antianginal activity, nicardipine showed a significantly greater anti-ischemic and hemodynamic activity at that time.We gratefully acknowledge the technical assistance of Chiara Pioselli in the performance of the exercise tests and preparation of this report.     

钙拮抗剂合心爽抑制动脉粥样硬化形成的实验研究

目的 观察合心爽对家兔动脉粥样硬化（AS）形成的抑制作用.方法 28只家兔随机分为正常对照组（CTRL）、单纯胆固醇喂饲组（CHOL）、维生素D3组（CHVD）（胆固醇喂饲＋维生素D3 50 000 U/kg,im,每2周1次）及合心爽组（CHDL）（胆固醇喂饲＋合心爽100 mg·kg-1·d-1）4组,分别于第15、45、84天对比检测血清脂质过氧化物（LPO）、超氧化岐化酶（SOD）、过氧化氢酶（CAT）浓度变化,实验12周结束后对比观察各组间胸主动脉组织钙含量和主动脉组织AS病理损伤程度.结果 各组主动脉钙含量与AS损伤程度均呈正相关.与CHOL组指标进行比较,CHVD组主动脉钙含量、血LPO含量、AS病理损伤指数均较高（均P＜0.01）,而血SOD、CAT活性则较低（均P＜0.01）;CHDL组LPO含量、AS损伤指标明显低于CHOL组（均P＜0.01）,SOD、CAT活性反而高于CHOL组（均P＜0.01）.结论 AS病理的发生发展与动脉组织钙含量的增加有关.合心爽能够抑制AS的形成,减少动脉壁钙含量,并可提高血清SOD、CAT的浓度.     

Flordipine, a calcium channel blocker, which does not influence lipidemia or atherosclerosis in cholesterol-fed rabbits

Data relating to the effects of calcium channel blockers on experimental atherosclerosis in rabbits are inconsistent with most studies finding no effect on either serum lipids or atherosclerosis. We have administered flordipine (5, 15 or 45 mg/kg/day) for 10 weeks to rabbits fed 1% cholesterol and 4% corn oil. At no level of treatment was there an effect on serum or liver lipids or on aortic sudanophilia.