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The effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide (PTLA) on lipid levels in serum and liver was compared with that of sitosterols in rats maintained on a diet supplemented with 1% of cholesterol, 0.5% of ox bile extracts, and 10% of hydrogenated coconut oil for 8 weeks. When PTLA was added to the diet at a level of 0.1%, the mean liver cholesterol level of male rats was reduced to 41% of the control and that of female rats was reduced to 19% of the control. In female rats, which showed higher cholesterol levels in serum and liver than male rats after cholesterol feeding, PTLA lowered the liver cholesterol level even at 0.0008% in the diet. Serum cholesterol was lowered by PTLA but not so markedly as liver cholesterol. The inhibition of cholesterol deposition in the liver suggests that the interference with cholesterol absorption is one of the main actions of PTLA. Sitosterols showed a similar pattern of lipid-lowering action, but the potency was far less than that of PTLA. more...

The concept that much of the cholesterol deposition in atherosclerotic plaque development is provided by ingress of blood-derived apo B-rich lipoproteins into the arterial intima is given support by the study of arterial apo B accumulation. To compare the arterial wall level of immunoreactive apo B during the progression of diet-induced atherosclerosis in two widely used animal models of atherosclerosis, rhesus and cynomolgus monkeys were fed an atherogenic diet for 4, 8, and 12 months and their abdominal aortas quantitated for apo B. Apo B was extracted from aortic intima-media homogenates in two forms: Tris-buffer extractable or 'loosely bounds' and detergent (Triton X-100) extractable or 'tightly bound'. The aortic extracts were quantitated for apo B by radial immunodiffusion, using goat anti-rhesus apo B along with serum LDL standards of the appropriate species diluted in the two extract solutions. The control monkeys' aortas contained only buffer-extractable apo B. The atherosclerotic aortas of both species of monkeys progressively increased their levels of loosely bound and tightly bound apo B through 4, 8, and 12 months of atherogenic diet feeding, with the 8- and 12-month cynomolgus aortas containing much larger amounts of apo B than the rhesus aortas. These differences in aortic apo B content could be accounted for by the greater rate at which the cynomolgus atherosclerotic lesions developed at the later time points. When the total lesion apo B levels were correlated with representative morphometrically-quantitated histopathologic sections of the homogenized aortas, a highly significant correlation was seen between the total aortic apo B values and both the absolute area of the intimal lesions and the total area of oil red O stainable lipid in the lesions (P less than 0.001). These data indicate that as atherosclerotic lesions become larger and richer in lipid with progression of the disease, the amount of apo B-associated lipoproteins which are deposited unmetabolized in the lesions increases. These lipoproteins are increased in both the tightly bound and loosely bound forms. more...

Nisoldipine (1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-yridineecarboxylate) ist a potent Ca2+ antagonist with a preferential effect on the vasculature. When administered rally (10 mg/kg body weight per day) nisoldipine reduces (P < 0.001) the meanarterial blood pressure (measured by the tail cuff method) in spontaneously hypertensive but not in normotensive Wistar Kyoto or Sprague Dawley rats. more...

Rabbits were maintained on a 1% cholesterol diet for 30, 60 and 90 days and jsotope labeling of aorta and serum was attained by feeding 100 mc of 4-14C-cholesterolduring the last 4 days before sacrifice of each group. Labeled aorta and low-density lipoprotéine (LDL) isolated from sera of the various diet regimens were employed for in vitro study of rates of flux of free and esterifiedcholesterol by incubating respectively with LDL and aorta of a rabbitmaintained for similar periods on above diet but given no radiocholesterol. Influx of free and ester cholesterol into thoracic aorta of hypercholesterolemia rabbit were respectively 6 and 11 times that obtained with tissues isolated from norraocholesterolemic animals. With progressive Ingestion of hypercholesterolemia diet, a gradual increase in rate of influx with concomitant lowering of efflux rate was noticed for both free and ester cholesterol. Studies on percentage clearance of labeled cholesterol from aorta of hypercholesterolemic rabbits into serum LDL indicate that 25 to 30 percent of radioactivity of free cholesterol is removed by LDL as against 2 to 4.5 percent of ester cholesterol radioactivity. Experiments carried out with partially de-lipidated LDL of sera hypercholesterolemic rabbits reveal that efflux of cholesterol from aorta is markedly increased. more...

The effects of vasectomy and exercise upon arterial extensibility, cholesterol deposition, and the extent of stainable tissue lipids were determined in rats. A 2 X 3 factorial design with two activity levels (treadmill exercise and sedentary) and three treatment levels (vasectomy, sham vasectomy and control) were employed. The exercise groups had significantly greater arterial extensibility measures at breaking load and stretch distance at 45% load and breaking point. The vasectomy-sedentary group had significantly less extensibility than the control-sedentary group for stiffness and stretch distance at 45% load and breaking point. Vasectomy significantly increased the amount of esterified and total cholesterol in aortic tissue. The vasectomy-sedentary group had significantly higher unesterified cholesterol levels than the three exercise groups. Total cholesterol levels were significantly higher for the sedentary groups than the exercise groups. There were no significant differences between groups in the extent of stainable tissue lipids. more...

The effects of saturated fat feeding as contrasted with unsaturated fats were studied in rats. The rats on unsaturated fat had lower serum cholesterol and less cholesterol deposition in the aorta, kidney, and liver than those on saturated fats. The animals on unsaturated fat had less deposition of orally fed 14C-cholesterol and iv Na-Ac in these organs than those on saturated fat. Evidence was adduced that the kidney is more efficient than the aorta in removing cholesterol on saturated fat diets. more...

Rats fed a high lipid diet and also exposed to unavoidable and unpredictable grid shock for 2 and 8 days showed higher levels of accumulated chemical cholesterol in aorta, kidney, liver and serum as compared to control rats fed only the high lipid diet. Thirty days of shock stress produced similar results except that kidney tissue revealed lower and nonsignificant levels of accumulated cholesterol. A differential cholesterol clearing mechanism for the various tissues is postulated to explain the relative vulnerability of aorta, liver and kidney to stress-induced cholesterol deposition. more...

SummaryCertain substances reactive with proteins have been found in vitro to cause selective adsorption of suspended cholesterol to the inner lining of hog aorta.

In a previous paper (1) it was found that stress had definite effects on lipid deposition in rats on high cholesterol diet. In that paper it was found that there was increased deposition of cholesterol in the aortas, livers, and sera of stressed animals as compared to the controls. There was only a transient elevation in the kidneys of the stressed antimals. Additionally, evidence was presented that the kidney had a better mechanism for clearing cholesterol than the aorta. Also, in other work it has been found that clofibrate seemed to have some effect in mobilizing cholesterol from tissues (2). In this paper an attempt was made to see if CPIB would have any effect on cholesterol deposition in the stressed rat. more...

1. 1. A study was done on the effect of stress on cholesterol deposition in various organs of pair-fed rats. 2. 2. There was an increased amount of cholesterol with aortas, livers, and serum of the stressed animals as compared to the control. 3. 3. There was only a transient elevation in the kidneys of the stressed animals. 4. 4. Evidence is presented that the kidney possesses a better mechanism for clearing cholesterol than the aorta. more...

A key role in the pathogenesis of atherosclerotic lesions is represented by cholesterol deposition in the arterial vessel wall, and a large body of international, randomised, controlled clinical trials have shown that the clinical use of drugs that are active in lowering serum cholesterol concentrations, such as competitive inhibitors of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase (collectively defined as 'statins'), produces significant reductions of cardiovascular mortality and morbidity through different and sometimes not fully elucidated mechanisms. However, it is important to consider that the patients who get the largest benefit from taking statins (frequently at high doses) are at the same time those with the highest risk of presenting adverse effects related to the use of these drugs. These patients are usually elderly, hypertensive and diabetic, often have renal function impairment or other associated clinical conditions and are usually receiving multiple therapies. Consequently, these patients may be exposed to adverse effects caused by pharmacological interactions of other drug classes with statins. Because of this, cardiologists need to be properly aware of the beneficial potential of these compounds but also of the potential limits and risks associated with the use of statins in the population at large.This article is aimed at examining the safety profile linked to the clinical use of statins and suggesting an adequate management to prevent the potential adverse effects while taking advantage of the outstanding cardiovascular benefits of statins. more...