Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries and platelets at various stages of experimental atherosclerosis in rabbits

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      Atherosclerosis was induced by feeding rabbits with 1 g of cholesterol and 3 g of olive oil daily for 1, 3 and 5 months. Arachidonic acid (AA)-induced generation of prostacyclin (PGI2) by perfused hearts and spontaneous generation of PGI2 by slices of mesenteric arteries and aortas were strongly suppressed after 1 and 3 months of the diet, while after 5 months a tendency for PGI2 synthesizing capacity to recover was observed. Aggregatability of blood platelets in platelet-rich plasma (PRP) by exogenous AA and endogenous thromboxane A2 (TXA2) was increased but not earlier than 3 months on the diet. On the other hand, platelet sensitivity to the pro-aggregatory action of adenosine diphosphate (ADP) and to the anti-aggregatory action of PGI2 was heightened as early as 1 month from the beginning of the experiment. These findings suggest that the first stage of experimental atherosclerosis may be causally related to the strong suppression of PGI2 generation by arteries, whereas the metabolism of AA in platelets remains unchanged. At this early stage of atherosclerosis increased susceptibility of platelets in PRP to both ADP and PG12 may be due to the lowering of cyclic AMP levels in platelets as a consequence of PGI2 deficiency. A genuine enhancement of AA metabolism in blood platelets occurs only at the second stage of experimental atherosclerosis. This stage is particularly dangerous since an increased generation of TXA2 by platelets in PRP is combined with a decreased generation of PGI2 by arteries. At the last stage of atherosclerosis observed, a slow recovery of the enzymic activity occurs in arteries.


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