ABSTRACT
In this work we investigated the influence of hyperlipemia on the fibrinolytic system and also attempted to determine whether vascular lesions may modify the response of plasminogen activators to hyperlipemia. The study was made on rats. Three different diets were administered to the animals, two of the diets only increased the levels of plasmatic lipids in the animals (hyperlipemic groups), but the third induced hyperlipemia and lipid infiltration in aorta (arteriosclerotic group). Fibrinolytic activity was evaluated in the plasma, on the aorta endothelial surface and in aorta wall. In the plasma, plasminogen activator (PA) activity was increased in the hyperlipemic and arteriosclerotic groups compared to control group, however, the activity of fibrinolysis inhibitors was also increased. On the endothelial surface and in the aorta wall, fibrinolytic activity was increased in the groups which received hyperlipidic diets but in the arteriosclerotic group only the endothelial surface showed a clear increase of fibrinolytic activity. A positive correlation was observed between PA activity and levels of hyperlipemia. However, no correlation has been shown between fibrinolytic activity in the aorta with cholesterol and triglyceride levels in this vascular wall.
Subject(s)
Arteriosclerosis/etiology , Fibrinolysis , Hyperlipidemias/blood , Animals , Aorta/metabolism , Arteriosclerosis/blood , Endothelium, Vascular/metabolism , Female , Lipid Metabolism , Plasminogen Activators/metabolism , Rats , Rats, Inbred Strains , Serum Globulins/metabolism , alpha-2-Antiplasmin/metabolismABSTRACT
The direct correlation between high circulating lipidic levels and the risk of suffering from atherosclerosis, together with the modification of different lipoproteic fractions in the development of this disease, has led us to study the characteristics of the hypolipemic effect of Plafibride. Experiments were carried out on a model of experimental arteriosclerosis in rats. The drug was administered at four dosage levels during induction of arteriosclerosis in order to establish a possible dose-effect relationship. Evaluation of the therapeutic activity was analyzed against the atherosclerotic control group. We found a marked hypolipemic activity and a strong increase in HDL-cholesterol, which reached normal levels. Consequently, Plafibride presents a profile of activity which can be considered suitable in the treatment of atherosclerosis.
Subject(s)
Arteriosclerosis/drug therapy , Clofibrate/analogs & derivatives , Clofibric Acid/analogs & derivatives , Hypolipidemic Agents/therapeutic use , Animals , Arteriosclerosis/blood , Cholesterol/blood , Cholesterol, HDL , Clofibric Acid/therapeutic use , Female , Lipoproteins, HDL/blood , Rats , Rats, Inbred Strains , Triglycerides/bloodABSTRACT
Hemorheological changes produced in blood cells seem to be essential in atheroma plaque development and thrombotic episodes. In this study, we investigated the relationship between blood cells count, thrombogenic situations and morphological mesenteric alterations in atherosclerotic rats. Atherosclerosis was induced by an atherogenic diet made up of two phases, the first a hypervitaminic diet, and the second a hyperlipidic one. Cell counts were performed with Thoma's camera. Morphological changes were observed directly in rat mesentery. Thrombogenic situations were investigated by a mesenteric microthrombosis induction method. In atherosclerotic animals we can observe a higher mesenteric opacity, increase in blood viscosity and a thickness in vessel wall. Thrombosis time is shortened at 3 days, which indicates a thrombogenic situation although at 10 days there is a lenthening in this parameter. Blood cell counts were not modified significantly, but modifications in differential leukocyte counts were significant. We found a direct relationship between lymphocyte number and thrombosis time whereas with granulocytes this relationship was inverse: shortening in thrombosis time appearing simultaneously with an increase in cell number.