HYPOCOAGULANT AND LIPID-LOWERING EFFECTS OF DIETARY N-3 POLYUNSATURATED FATTY-ACIDS WITH UNCHANGED PLATELET ACTIVATION IN RATS

We investigated the effects of dietary polyunsaturated fatty acids (PU FAs) on blood lipids and processes that determine hemostatic potential : platelet activation, coagulation, and fibrinolysis. For 8 to 10 week s, Wistar rats were fed a high-fat diet containing various amounts (2% to 16%) of n-3 PUFAs derived from fish oil (FO) or a diet enriched in n-6 PUFAs from sunflower seed oil (SO). Only the FO diets caused a re duction in mean platelet volume, platelet arachidonate level, and form ation of thromboxane B-2 by activated platelets, but neither of the di ets had a measurable effect on platelet activation. The FO-rich diets decreased the plasma concentrations of triglycerides and cholesterol, whereas the SO diet reduced triglycerides only. Parameters of fibrinol ysis and standard coagulation times, ie, activated partial thromboplas tin time and prothrombin time, were only marginally influenced by thes e diets. In contrast, dietary FO, but not SO, led to decreased levels of the vitamin K-dependent coagulation factors prothrombin and factor VII, while the level of antithrombin III was unchanged. The endogenous thrombin potential (ETP) was measured with an assay developed to dete ct the hypocoagulable state of plasma. After activation with tissue fa ctor and phospholipids, the ETP was reduced by 23% or more in plasma f rom animals fed a diet with >4% FO. No significant effect of the SO di et on ETP was observed. Control experiments with plasma from warfarin- treated rats indicated that the ETP was more sensitive to changes in p rothrombin concentration than in factor VII concentration. Taken toget her, these results indicate that in rats, prolonged administration of n-3 but not n-6 PUFAs can lead to a hypocoagulable state of plasma thr ough a reduced capacity of vitamin K-dependent thrombin generation, wi th unchanged thrombin inactivation by antithrombin III.