Modulation of rat platelet activation by vessel wall-derived prostaglandinand 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 de creased levels of arachidonate and increased levels of eicosapentaenoate an d docosahexaenoate. These diet-induced changes were accompanied by a reduce d formation of thromboxane A(2) (TXA(2)) and prostaglandin I-2 (PGI(2)) in platelets and aortic tissue, respectively. When platelets were incubated wi th autologous, aorta-derived PGI(2), the dietary modulation of PGI(2) gener ation had a stronger effect on the activation process than the dietary effe ct on TXA(2) generation. The platelet-inhibiting effect of PGI(2) was indep endent of the type of agonist and involved both TXA(2)-dependent and -indep endent activation responses. PGI(2) also inhibited the agonist-induced form ation 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 con clude 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 caus ed by an altered thromboxane-prostaglandin balance. (C) 2001 Elsevier Scien ce Ireland Ltd. All rights reserved.