Relationship between serum cholesterol and thromboxane B2 levels and atherosclerotic lesions in rabbits fed a high cholesterol diet

The aim of our study was to evaluate the effects of diet induced hypercholesterolemia and associated atherosclerosis in rabbits on serum thromboxane B2 levels. We have determined thromboxane B2 in serum of hypercholesterolemic rabbits with atherosclerosis and in normocholesterolemic rabbits without atherosclerosis. Our data show only a mildly higher serum thromboxane levels in hypercholesterolemic rabbits and extensive atherosclerosis than in controls without atherosclerosis. In conclusion, these results show that diet induced hypercholesterolemia was not associated with thromboxane B2 generation, in spite of a diffuse experimental atheromatosis.     

The effect of fish oil on atherogenesis and thrombopoiesis in rabbits on high cholesterol diet

The effect of fish oil supplementation on atherogenesis and thrombopoiesis was investigated in rabbits fed a high cholesterol diet for 7 weeks. There was no statistically significant difference between the area of lipid accumulation in the aorta of the animals fed fish oil and the control animals. There was no statistically significant difference in platelet count, mean platelet volume, megakarycoyte DNA content or serum cholesterol between the two groups. Serum triglyceride was significantly higher in the fish oil group than in the controls (p less than 0.035). Fish oil supplementation does not change atherogenesis or thrombopoiesis in the cholesterol fed rabbit.     

姜黄素对食高脂饲料家兔血管内皮功能的保护作用

目的　观察姜黄素对高脂血症家兔血管内皮功能的保护作用。方法　 36只雄性新西兰大白兔随机分为3组 ,即对照组 (喂普通饲料 )、模型组 (喂普通饲料 +1 5 %胆固醇、5 %的猪油 )和姜黄素组 (喂普通饲 +1 5 %胆固醇、5 %的猪油 +姜黄素 5 0mg·kg-1·d-1)。试验 4周后采血行血脂分析 ,酶法测NO ,放免法测ET 1,Elisa法测vWF ;采用离体血管功能实验方法 ,分别观察预先用苯肾上腺素作为收缩剂处理后的各组降主动脉血管环对乙酰胆碱和硝酸甘油的舒张反应。结果　姜黄素组血清TC、LDL C、TG及ET 1、vWF水平明显下降 ,NO水平明显增高 ,与模型组比较差别显著性(P <0 0 5 ) ;与对照组比较 ,模型组降主动脉血管环对乙酰胆碱 (3× 10 -7～ 3× 10 -5mol/L)刺激的舒张反应下降 ;姜黄素组血管环对乙酰胆碱刺激的舒张反应明显改善 ,与模型组比较有显著差别。三组血管环对不同浓度的硝酸甘油刺激的舒张反应无差异 (P >0 0 5 )。结论　姜黄素能纠高脂血症家兔内皮血管活性物质的紊乱 ,改善内皮依赖性舒张功能 ,对血管内皮功能有保护作用。     

Lack of effect of probucol on atheroma formation in cholesterol-fed rabbits kept at comparable plasma cholesterol levels

Rabbits were fed cholesterol for 14 weeks to study the effect of probucol on atheroma formation. Three groups of animals were investigated: group CHOL was fed 1% cholesterol and served as control for group P + CHOL. fed 1% cholesterol and 1% probucol from the onset till the end of the experiment: group CHOL + P received 1% cholesterol throughout the experiment and 1% probucol during the last 4 weeks only. Plasma cholesterol concentrations were monitored at frequent intervals and were modulated by dietary perturbations so that the areas under the curve expressing plasma cholesterol changes with time, were similar in probucol and non-treated rabbits. The efficacy of long-term probucol treatment was evidenced by a significant reduction in plasma apolipoprotein A-I throughout the experiment and lower plasma TBARs during the first 6 weeks, when the hypocholesterolemic effect of probucol was also seen. Two weeks prior to the termination of the experiment, the rabbits were injected with rabbit plasma labeled with [3H]cholesteryl linoleyl ether [( 3H]CLE). Aortic atheromatosis was quantified by determination of total and cholesteryl ester (CE). The aortic cholesterol content was related to the arch, thoracic and abdominal segments, to the surface area of each segment or its dry defatted weight. Total and esterified cholesterol were highest in the aortic arch in all 3 groups when related to any of the above mentioned parameters. No statistically significant difference in aortic total cholesterol and CE content was seen among the three groups studied. The [3H]CLE recovered in the aortic segment correlated with the CE content and the [3H]CLE (dpm)/mg CE in all segments was similar. No statistically significant difference in the [3H]CLE recovered in the aortic segments among the 3 groups was seen. We conclude that in cholesterol-fed rabbits, in which the plasma cholesterol levels were maintained at comparable levels, probucol treatment did not affect plasma CE influx into the aorta and did not attenuate development of aortic atherosclerosis.     

Probucol reduces plasma and aortic wall oxysterol levels in cholesterol fed rabbits independently of its plasma cholesterol lowering effect.

To understand further the antiatherogenic mechanism of probucol, the antioxidant effect of this agent was studied on specific cholesterol oxidation products in plasma and aortic wall in equally hypercholesterolemic New Zealand white rabbits. In order to maintain equal plasma total cholesterol levels, five control rabbits (C group) received a 1% followed by a 0.5% cholesterol enriched diet, while the probucol treated rabbits (C+P group) received a graded increase in the cholesterol supplemented diet from 1% to 3%; probucol supplementation was constant at 1%. After 9 weeks of feeding, the plasma oxysterols, cholest-5-ene-3 beta,7 alpha-diol, cholest-5-ene-3 beta,7 beta-diol, 5,6 beta-epoxy-5 alpha-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 alpha-ol and 5 alpha-cholestane-3 beta,5,6 beta-triol significantly increased over baseline levels in both experimental groups. However, the increase in all these products in plasma was 20-60% less in the C+P group than the C group (P < 0.05). Furthermore, the C+P aortic wall cholesterol oxide concentrations were 50-90% less than the C group (P < 0.05). The oxysterol pattern of the aortic wall was similar to plasma. Additionally, the aortic wall cholesterol content in the C+P group was 50% less than the C group (P < 0.05). The plasma cholesterol levels were not significantly different at any time point during the study and the cholesterol oxide content in the diets was the same. These results are consistent with the contention that the antioxidant properties of probucol serve as the basis for its antiatherogenic effects in vivo.     

Lack of effect of chronic hypocalcaemia on serum prolactin response to chlorpromazine

The effects of chronic hypocalcaemia on serum basal and chlorpromazine-stimulated prolactin (Prl) levels were studied in 16 patients with idiopathic or secondary hypoparathyroidism. These results were compared with the results of other chlorpromazine stimulation tests which were made in the normocalcaemic state after treatment with vitamin D, and in normal subjects. In hypocalcaemic and normocalcaemic states (mean serum Ca 5.8 +/- 0.24 mg/dl and 9.5 +/- 0.11 mg/dl, respectively) basal Prl levels were within the normal range and during stimulation the maximal stimulated levels in each state were not significantly different from each other. Also, the mean serum Prl levels obtained from a control group were not different from values in the normocalcaemic state. It is concluded that chronic hypocalcaemia does not inhibit Prl secretion and low serum parathyroid hormone levels do not affect basal and chlorpromazine-stimulated Prl secretion.     

低强度氦氖激光血管内照射对家兔血栓素、前列环素及脂质过氧化物的影响

通过观察低强度氦氖激光血管内照射（ILLLI）对饲脂家兔血浆中血栓素B2（TxB2）、6-酮-前列腺素F1α（6－keto－PGF1α）、脂质过氧化物（LPO）、TxB2／6-keto－PGF1α及主动脉和冠状动脉病理学改变，探讨ILLLI预防动脉粥样硬化（AS）的机制。结果表明：ILLLI可显著降低TxB2、LPO及TxB2／6－keto－PGF1α（P＜0.01），而对6-keto-PGF1α无升高作用（P＞0．05）。主动脉粥样斑块面积百分比与TxB2、LPO呈显著正相关（r=0．8641，P＜0．01），与6-keto－PGF1α是显著负相关（r=-0.7432，P＜.05）。光镜观察，ILLLI治疗后主动脉及冠状动脉粥样斑块病变程度明显减轻。提示：ILLLI具有预防AS的作用。     

The effects of mevinolin on serum cholesterol levels of rabbits with endogenous hypercholesterolemia

Mevinolin, a fungal metabolite isolated from cultures of Aspergillus terreus, is a potent competitive inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis. In the current studies we demonstrate that mevinolin significantly lowers serum cholesterol in rabbits fed a cholesterol free, low-fat semi-synthetic diet. Rabbits maintained on this diet developed endogenous hypercholesterolemia with average cholesterol concentrations of 310 mg/dl over a 66-day period. Treatment with mevinolin for 39 days at a dose of 2 mg/kg per day lowered serum cholesterol levels by an average of 37% (P less than 0.05), while a dose of 6 mg/kg per day resulted in a 48% (P less than 0.05) decrease when compared with the control group. When the administration of mevinolin was discontinued, serum cholesterol levels of the 6 mg/kg per day group increased significantly to a maximum post-treatment value of 319 mg/dl (P less than 0.0001). The results of this study demonstrate that rabbits with endogenous hypercholesterolemia are a useful animal model for the study of cholesterol biosynthesis inhibitors like mevinolin.     

Verapamil and diet halt progression of atherosclerosis in cholesterol fed rabbits

Summary The present study was designed to evaluate the effects of oral verapamil and normal diet on regression of atherosclerotic plaque in cholesterol fed rabbits. Forty-three rabbits were separated into 6 groups and studied for 24 weeks. All groups had a cholesterol diet for the first 12 weeks. Group I was then sacrificed and had 38±23% (mean ± standard deviation) aortic plaque. During weeks 13 to 24, group II (cholesterol diet) and group III (normal diet) had similar percentages of aortic plaque: 80±7% and 78±22%, respectively. Group IV (cholesterol diet), was treated with oral verapamil for 24 weeks and had significantly less plaque (54±10%) than group II, (80±7%). In group V (cholesterol diet), treatment with oral verapamil during weeks 13 to 24 did not significantly reduce plaque (70±23%), compared to group II, (80±7%). In group VI, normal diet and verapamil during weeks 13 to 24 significantly reduced aortic plaque (46±25) when compared to group II (80±7%). Group VI (46%) did not differ from group I (38%). It is concluded that verapamil combined with a normalized diet can halt the progression of aortic atherosclerosis after a 12 week atherogenic diet in rabbits. Verapamil or diet alone was ineffective in the second 12 weeks. Overall, verapamil was effective in preventing atherosclerosis but was ineffective in causing regression of atherosclerosis.Supported in part by Susan and Don Schleicher and the George D. Smith Fund.