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 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.
Nieuwenhuys
C M
CM
Department of Human Biology, University of Maastricht, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Feijge
M A
MA
Offermans
R F
RF
Kester
A D
AD
Hornstra
G
G
Heemskerk
J W
JW
D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016718:Arachidonic Acid / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D011464:Epoprostenol / Q000378:metabolism*; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005395:Fish Oils / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D015539:Platelet Activation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D013928:Thromboxane A2 / Q000378:metabolism*; D014280:Triglycerides / Q000494:pharmacology*
D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D000960:Hypolipidemic Agents; D014280:Triglycerides; C077446:Pikasol; D016718:Arachidonic Acid; D013928:Thromboxane A2; D011464:Epoprostenol; D002118:Calcium