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1. The main objective of the present study was to verify the speed with which two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, simvastatin and pravastatin, could revert endothelial cell dysfunction in hypercholesterolaemic rabbits. An attempt was also made to correlate the plasma cholesterol level and the tissue cholesterol and malondialdehyde (MDA) contents of the aortae with the endothelium-dependent relaxation on the assumption that any endothelial dysfunction could be rapidly and partially reversed, even in the presence of relatively high serum cholesterol levels. 2. Ninety-one male New Zealand white rabbits were randomly assigned to hypercholesterolaemic (control), simvastatin or pravastatin groups. All rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for 8 weeks. Simvastatin (10 and 20 mg/day) and pravastatin (15 and 30 mg/day) were administered 6, 4 and 2 days before the end of the experiment. At the end of the 8th week, animals were killed and the aortae were removed for histological examination as well as for the measurement of cholesterol and MDA contents and for endothelium-dependent relaxation studies. 3. The results showed that significant improvement in endothelium-dependent relaxation was obtained only with pravastatin and only with 4 or 6 days of administration. In these cases, the cholesterol and MDA contents of the vessel wall were reduced, although no significant changes were observed in plasma total cholesterol. Higher doses of the drugs did not alter these results. 4. We conclude that pravastatin enhances endothelium-dependent relaxation when administered to cholesterol-fed rabbits, probably via an anti-oxidant action. This effect, which was observed to start on the 4th day of drug administration, may represent a new therapeutic approach for the treatment of acute coronary syndromes in hypercholesterolaemic patients.

1. The aim of this study was to evaluate the role of endothelium in mediating the response to acetylcholine in the thoracic aorta and coronary vessels of rats exposed to cigarette smoking. Total serum cholesterol was measured at the beginning and end of the experiment. 2. The relaxation response to acetylcholine was significantly impaired in the aortae of rats exposed to cigarette smoking (P < 0.05); and the coronary flow during the administration of acetylcholine (0.02 microgram/min.) was significantly reduced (P < 0.05). The total cholesterol plasma levels increased 31.13% in those exposed to smoke when compared to the controls (P < 0.05). 3. It is concluded that exposure to cigarette smoking increases total serum cholesterol levels, and also produces primary endothelial dysfunction in aorta rings and coronary vessels.

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The authors studied the effect of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs. Adult mongrel dogs weighing 7.4 +/- 1.0 kg were divided into control, hypercholesterolemic and vitamin E groups. The animals in the hypercholesterolemic group were fed a diet enriched with cholesterol (5% w/w) and coconut oil (10% w/w) for 40 days. The vitamin E group received the same diet plus 400 IU of vitamin E during the last 15 days of the experiment. Total serum cholesterol levels were evaluated at the beginning and at the end of the experiment using a commercial enzyme kit and a Beckman analyzer. The coronary flow was determined by electromagnetic flowmetry using a probe positioned in the left anterior descending coronary artery, near the ostium. A needle connected to a perfusion pump was introduced into the coronary artery for the administration of acetylcholine and sodium nitroprusside at a rate of 5 micrograms/kg per min. The aorta was cannulated for the measurement of arterial blood pressure via a pressure transducer coupled to a Siemens multi-channel recorder. The tissue cholesterol content and malonic dialdehyde (MDA) were also measured in isolated coronary vessel specimens. At the end of 40 days, the serum cholesterol levels had increased by 226% and 190% in the hypercholesterolemic and vitamin E groups, respectively. However, the difference in the levels of these two groups was not significant (P > 0.05). The aortic blood pressure and heart rate remained unchanged during acetylcholine administration. In contrast, systolic and diastolic pressure fell and the heart rate increased during the infusion of sodium nitroprusside. The tissue cholesterol content and MDA were significantly (P < 0.05) increased in coronary artery specimens from the hypercholesterolemic compared to control animals. Vitamin E was able to reduce these increases in cholesterol treated animals (P < 0.05). The percent change in coronary flow during acetylcholine administration was significantly lower in the hypercholesterolemic group when compared with control animals (P < 0.05) but was unaltered in the vitamin E group (P > 0.05). During sodium nitroprusside administration, the coronary flow increased in the vitamin E group (P < 0.05). The authors conclude that hypercholesterolemia reduces endothelium-dependent coronary flow and increases the tissue cholesterol content and MDA of coronary arteries. Vitamin E decreases the MDA and the tissue cholesterol content without significantly affecting the total serum cholesterol level. Vitamin E may thus restore coronary flow by reverting endothelial dysfunction.