Michiko Regina Ozaki

ENDOTHELIAL DYSFUNCTION IN CORONARY VESSELS AND THORACIC AORTA OF RATS EXPOSED TO CIGARETTE SMOKE

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.

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.

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.

Evolution and involution of atherosclerosis and its relationship with vascular reactivity in hypercholesterolemic rabbits

BACKGROUND AND OBJECTIVES The aim of this study is to verify the evolution and involution of experimental atherosclerosis in rabbits through the study of endothelial function, lipids and tissue lipid peroxidation, macro and microscopic quantification of aortic atherosclerosis. METHODS Thirty male New Zealand white rabbits were divided into six groups (n=5): G1 normal diet; G2: hypercholesterolemic receiving 0.5% of cholesterol diet for 4 months; G3: hypercholesterolemic diet for 4 months after normal diet for more 4 months; G4: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 1 month, G5: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 2 months, G6: hypercholesterolemic diet for 4 months plus normal diet and rosuvastatin for 4 months. Rosuvastatin was administered at a dosage of 5mg dissolved in 150 ml of water daily. At the end of the experiment were measured: total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), tissue cholesterol (CAO), lipid peroxidation tissue (MDA). Endothelial function (RMAX) was studied in a segment of thoracic aorta, through curve-effect of acetylcholine and sodium nitroprusside. The amount of atherosclerosis was determined by measurement of the arterial lesion, through software, after staining with Sudan IV and histological staining. RESULTS In relation the water the rabbits drank 60-70 ml all day. It was seen significantly increase in all parameters at G2 both biochemical and tissue. In the group G3 it was seen significantly decrease in plasma lipids levels and tissue cholesterol. Treated groups G4, G5 and G6 all showed a decreased plasma lipid levels, only at G6 group it was noted a tissue cholesterol, tissue peroxidation and quantification of atherosclerosis, which showed a significant decrease. In relation the endothelial function only G6 improve significantly. INTERPRETATION AND CONCLUSIONS Our findings indicated that the treatment with rosuvastatin for 4 months is more efficient because improve the endothelial function significantly.

Endothelial dysfunction, lipid peroxidation and cholesterol level in rabbit arteries: relationship to progressive hypercholesterolemia

Objective The aim of this study was to evaluate the influence of a gradual increase in the plasma total cholesterol concentration and of lipid peroxidation on endothelial function in rabbit arteries. Material and methods Fifty male New Zealand white rabbits were fed a diet enriched with 0.5% cholesterol and 10% coconut oil and were allocated to one of nine groups (G2 to G10) based on sequential determinations of their plasma total cholesterol concentration (each group covered an interval of 100 mg/dL). The control group (G1) consisted of five rabbits fed a non-supplemented diet. The rabbits were killed at the end of the treatment and the total plasma cholesterol concentration, arterial wall cholesterol level and lipid peroxidation based on the quantification of malondialdehyde were determined using commercial kits. Endothelial function was assessed based on concentration-response curves to acetylcholine and sodium nitroprusside in aortic segments. Results Treatment with a cholesterol-rich diet resulted in disproportional increases in the arterial wall cholesterol concentration, lipid peroxidation and a disproportional decrease in the maximum endothelium-dependent relaxations in relation to the plasma total cholesterol concentration. However, the maximum endothelium-dependent relaxations were proportional to the increase in the arterial wall content of malondialdehyde. Conclusions These results show that the levels of arterial wall cholesterol, lipid peroxidation and endothelial dysfunction are not proportional to the degree of hypercholesterolemia, although endothelial dysfunction is proportional to the extent of lipid peroxidation in the vessel wall.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

Background In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Effect of Pitavastatin on Vascular Reactivity in Hypercholesterolemic Rabbits

Background Pitavastatin is the newest statin available in Brazil and likely the one with fewer side effects. Thus, pitavastatin was evaluated in hypercholesterolemic rabbits in relation to its action on vascular reactivity. Objective To assess the lowest dose of pitavastatin necessary to reduce plasma lipids, cholesterol and tissue lipid peroxidation, as well as endothelial function in hypercholesterolemic rabbits. Methods Thirty rabbits divided into six groups (n = 5): G1 - standard chow diet; G2 - hypercholesterolemic diet for 30 days; G3 - hypercholesterolemic diet and after the 16th day, diet supplemented with pitavastatin (0.1 mg); G4 - hypercholesterolemic diet supplemented with pitavastatin (0.25 mg); G5 - hypercholesterolemic diet supplemented with pitavastatin (0.5 mg); G6 - hypercholesterolemic diet supplemented with pitavastatin (1.0 mg). After 30 days, total cholesterol, HDL, triglycerides, glucose, creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were measured and LDL was calculated. In-depth anesthesia was performed with sodium thiopental and aortic segments were removed to study endothelial function, cholesterol and tissue lipid peroxidation. The significance level for statistical tests was 5%. Results Total cholesterol and LDL were significantly elevated in relation to G1. HDL was significantly reduced in G4, G5 and G6 when compared to G2. Triglycerides, CK, AST, ALT, cholesterol and tissue lipid peroxidation showed no statistical difference between G2 and G3-G6. Significantly endothelial dysfunction reversion was observed in G5 and G6 when compared to G2. Conclusion Pitavastatin starting at a 0.5 mg dose was effective in reverting endothelial dysfunction in hypercholesterolemic rabbits.