Modulation of rat platelet activation by vessel wall-derived prostaglandin and platelet-derived thromboxane: effects of dietary fish oil on thromboxane–prostaglandin balance

By dietary manipulation of rats with n-3 polyunsaturated fatty acids (PUFAs), platelets and endothelium-containing aortic tissue were obtained with decreased levels of arachidonate and increased levels of eicosapentaenoate and docosahexaenoate. These diet-induced changes were accompanied by a reduced formation of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) in platelets and aortic tissue, respectively. When platelets were incubated with autologous, aorta-derived PGI2, the dietary modulation of PGI2 generation had a stronger effect on the activation process than the dietary effect on TXA2 generation. The platelet-inhibiting effect of PGI2 was independent of the type of agonist and involved both TXA2-dependent and -independent activation responses. PGI2 also inhibited the agonist-induced formation of TXA2. In addition, the platelet-inhibitory effect of PGI2 was more prolonged in time than the brief, stimulatory effect of TXA2. We conclude that, in the thromboxane–prostaglandin balance of platelet activation, PGI2 plays a more prominent role than TXA2. Furthermore, dietary n-3 PUFAs appear to influence platelet activation more by reducing formation of endothelial PGI2 than by decreasing autocrine-produced TXA2. Thus, in rats, the proposed antithrombotic effect of fish oil is unlikely to be caused by an altered thromboxane–prostaglandin balance.