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

Abstract

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 A 2 (TXA 2) and prostaglandin I 2 (PGI 2) in platelets and aortic tissue, respectively. When platelets were incubated with autologous, aorta-derived PGI 2, the dietary modulation of PGI 2 generation had a stronger effect on the activation process than the dietary effect on TXA 2 generation. The platelet-inhibiting effect of PGI 2 was independent of the type of agonist and involved both TXA 2-dependent and -independent activation responses. PGI 2 also inhibited the agonist-induced formation of TXA 2. In addition, the platelet-inhibitory effect of PGI 2 was more prolonged in time than the brief, stimulatory effect of TXA 2. We conclude that, in the thromboxane–prostaglandin balance of platelet activation, PGI 2 plays a more prominent role than TXA 2. Furthermore, dietary n-3 PUFAs appear to influence platelet activation more by reducing formation of endothelial PGI 2 than by decreasing autocrine-produced TXA 2. Thus, in rats, the proposed antithrombotic effect of fish oil is unlikely to be caused by an altered thromboxane–prostaglandin balance.