Paulo Afonso Ribeiro Jorge

Efeito da berinjela sobre os lípides plasmáticos, a peroxidação lipídica e a reversão da disfunção endotelial na hipercolesterolemia experimental

PURPOSE: To study the effect of egg plant on endothelium-dependent relaxation, and plasma lipids in hypercholesterolemic rabbits, and to assess influence of this plant on the malondialdehyde (MDA) content of LDL particles and the arterial wall. METHODS: Thirteen male rabbits were randomly assigned to control (C), hypercholesterolemic (H) and egg plant (E) treated groups (n=10 each). The H and E rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (10%) for 4 weeks. In addition, group E received 10mL of the fruit juice/day during the last 2 weeks.The animals were killed and the aorta removed to measure MDA content and the endothelium dependent relaxation responses. Total plasma cholesterol, VLDL, LDL, HDL and triglyceride levels were determined using commercial kits. MDA was quantified in native and oxidized LDL and in the arterial wall. RESULTS: After 4 weeks, the E group rabbits had a significantly lower weight , plasma cholesterol, LDL, triglyceride and aortic cholesterol contentthan group H(p<0.05). The MDA content that was significantly increased in the LDL particles and in the arterial wall of H rabbits was reduced in the E group (p<0.05). Endothelium-dependent relaxation were significantly higher in the E group compared H group rabbits (p<0.05). CONCLUSION: In hypercholesterolemic rabbits egg plant juice significantly reduced weight, plasma cholesterol levels, aortic cholesterol content and the MDA concentrations in native-oxidized LDL and in the arterial wall and increased the endothelium-dependent relaxations.

RAPID REVERSAL OF ENDOTHELIAL DYSFUNCTION IN HYPERCHOLESTEROLAEMIC RABBITS TREATED WITH SIMVASTATIN AND PRAVASTATIN

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.

Effects of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs

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.

Effects of Simvastatin and Pravastatin on endothelium-dependent relaxation in hypercholesterolemic rabbits

OBJECTIVES The present study was conducted to investigate endothelium-dependent relaxation in hypercholesterolemic rabbits after treatment with two HMG-CoA reductase inhibitors: Simvastatin and Pravastatin. METHODS Thirty male New Zealand rabbits were randomly assigned to Control, Simvastatin and Pravastatin groups and fed a diet supplemented with lipids and cholesterol (coconut oil 10% and cholesterol 1%) for 8 weeks. The drugs were administered in dosages of 10 mg/kg from the fourth to seventh weeks; at the end of the seventh week, plasma cholesterol was determined, and the Pravastatin dosage adjusted to 15 mg/kg to obtain similar levels of plasma cholesterol for the two experimental groups. At the end of the 8th week, the animals were killed and aorta removed for histologic examination and the measurement of cholesterol content, as well as for the conduction of endothelium-dependent relaxation studies. RESULTS At the end of the study serum cholesterol was reduced by 57.1% in the Pravastatin group and 58.4% in the Simvastatin group, with the aortic cholesterol content in the former being significantly lower than that of the Simvastatin and Control groups (p < 0.05). Histologic examination also revealed a significant decrease in volume fractions of foam cells in Pravastatin-treated animals, whereas endothelium-dependent relaxation in response to ACh was significantly impaired in the Simvastatin group. No significant difference was found in relaxation induced by nitroprusside. CONCLUSIONS In spite of the similar reduction in plasma cholesterol obtained by different doses, it seems that Pravastatin preserves the endothelium-dependent relaxation of aortic rings of hypercholesterolemic rabbits more effectively than does Simvastatin.

Improvement in the endothelium-dependent relaxation in hypercholesterolemic rabbits treated with vitamin E

The authors studied the time course of the vitamin E mediated improvement in endothelium-dependent relaxation in hypercholesterolemic rabbits. A total of 40 male New Zealand white rabbits were randomly assigned to hypercholesterolemic (control) and vitamin E treated groups. The latter group was further divided in three subgroups in accordance with the duration of the vitamin E treatment (2, 4 or 6 days) at the end of the experiment. The dose of vitamin E utilized was 50 IU/day administered once a day by gavage. All the rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for 4 weeks. At the end of this period, the animals were sacrificed and the aorta removed for determination of the cholesterol and malondialdehyde (MDA) contents. The relaxation of the aortic strips in response to acetylcholine was also studied. In addition, the cholesterol and MDA contents of native and oxidized LDL were measured. At the end of the 4th week, the MDA level was significantly reduced in native and oxidized LDL in the rabbits treated with vitamin E for 2 days, while in aortic tissue a reduction was seen after 4 days of treatment. Endothelium-dependent relaxation improved significantly after 6 days of vitamin E administration, and there was a reduction in the total plasma and aortic cholesterol levels during this same period. We conclude that vitamin E at a dose of 50 IU/day for 6 days improves the endothelium-dependent relaxation seen in hypercholesterolemic rabbits. This effect may be mediated through an antioxidant action on LDL particles and on the aortic arterial wall.

Effects of Atorvastatin, Fluvastatin, Pravastatin, and Simvastatin on Endothelial Function, Lipid Peroxidation, and Aortic Atherosclerosis in Hypercholesterolemic Rabbits

OBJECTIVE To compare the effects of atorvastatin, fluvastatin, pravastatin, and simvastatin on endothelial function, aortic atherosclerosis, and the content of malondialdehyde (MDA) in native and oxidized LDL and in the arterial wall of hypercholesterolemic rabbits after adjusting the dosages of those statins to reduce total serum cholesterol levels to similar values. METHODS Male rabbits were divided into the following 6 groups of 10 animals (n=10): 1) GH (control)--hypercholesterolemic animals; 2) GA--atorvastatin; 3) GF--fluvastatin; 4) GP--pravastatin; 5) GS--simvastatin; and 6) GN--normal. The animals were fed a standard food preparation enriched with 0.5% cholesterol and 2% coconut oil for 45 days. Fifteen days after beginning the experiment, atorvastatin, fluvastatin, pravastatin and simvastatin were administered for 15 days through gavage, and the dosages were adjusted to obtain similar cholesterol values in each group. At the end of the experiment, a blood sample was withdrawn for determining total cholesterol and separating the lipoproteins, and a segment of the thoracic aorta was removed to be used for studying endothelial function and lipid peroxidation, and for measuring aortic atherosclerosis in histological sections. RESULTS The statins significantly reduced total serum cholesterol levels, LDL-cholesterol levels, and aortic atherosclerosis. The MDA content was also significantly reduced in native and oxidized LDL, as well as in the arterial wall. Endothelium-dependent relaxation was significantly greater in the treated group compared with that in the hypercholesterolemic group. CONCLUSION The statins, at dosages adjusted, had a significant and similar effect in reducing lipid peroxidation in native and oxidized LDL-C and in arterial walls, in decreasing aortic atherosclerosis, and in reverting endothelial dysfunction.

Endothelium-dependent coronary flow in ischemia reperfusion

The aim of the present report was to study the effect of ischemia-reperfusion on the endothelial cell function of coronary vessels. Twelve adult male dogs were instrumented for the measurement of aortic and left ventricular pressures, heart rate and coronary blood flow. The left anterior descending coronary artery was occluded for 90 minutes followed by 20 minutes of reperfusion. Acetylcholine was infused into the coronary artery at a rate of 15 micrograms/kg/min. Coronary flow, heart rate and aortic and left ventricular pressures were registered during the pre-occlusion period and after 20 minutes of reperfusion under basal conditions, as well as during acetylcholine administration. These same parameters were also measured during reactive hyperemia following vessel deocclusion. Acetylcholine produced a 155% increasing coronary flow during the pre-occlusion period (p < 0.05). In the reperfusion period, no statistically significant difference was observed between the flows in the presence and absence of this substance, nor were there any differences in the other cardiovascular parameters monitored. Triphenyltetrazolium staining confirmed myocardial infarction in all the hearts examined. The authors conclude that reperfusion following myocardial infarction prevents the increasing in coronary flow in response to acetylcholine as a result of endothelial dysfunction in the resistance coronary vessels.

Efeito dos ácidos graxos ômega-3 sobre o relaxamento-dependente do endotélio em coelhos hipercolesterolêmicos

PURPOSE: To study the effect of omega-3 fatty acid on endothelium-dependent relaxation, total plasma cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides levels as well as, the malondialdehyde (MDA) content of the LDL particles and arterial wall. METHODS: Fourteen male rabbits were randomly assigned to hypercholesterolemic and omega-3 groups. The dose of omega-3 fatty acid utilized was 300g/kg/day during 15 days. All rabbits were fed a diet supplemented with cholesterol (0.5%) and coconut oil (2%) for four weeks. At the end of the experiment the animals were killed and the aorta removed for measurement of MDA content and the endothelium-dependent relaxation studies. Total plasma cholesterol, VLDL-cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides was measured by enzymatic kits. MDA was also measured in natives and oxidized LDL and arterial wall. RESULTS: Cholesterol and VLDL-cholesterol were increased significantly in the omega-3 treated animals. The triglyceride level was significantly reduced (p<0.05). The MDA content was increased in the LDL particles and in the arterial wall (p<0.05). Endothelium-dependent relaxation was significantly reduced (p<0.05). CONCLUSION: Omega-3 fatty acid impairs the endothelium-dependent relaxation when administered to cholesterol fed rabbits, increases the cholesterol and reduces the triglycerides plasma levels. The lipid peroxidation of the LDL particles and arterial wall was increased.