Aspirin and indomethacin enhance platelet aggregation in mouse mesenteric arterioles.
The cyclooxygenase inhibitors aspirin and indomethacin enhanced platelet aggregation in mesenteric vessels, suggesting that the normal mesentery produces an antiaggregatory prostaglandin. Testing of mesentery incubate in mouse platelet-rich plasma disclosed an antiaggregatory material with the properties of prostacyclin. Chromatography showed that mesentery made several radiolabeled products from [3H]arachidonic acid, including one that cochromatographed with 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable hydrolysis product of prostacyclin. Gas chromatography-mass spectrometric analysis of mesentery incubate showed the presence of 6-keto-PGF1 alpha, synthesized from the mesentery's endogenous arachidonic acid. The enhancement of platelet aggregation in mesenteric vessels contrasts with earlier data showing that in similarly injured mouse cerebral vessels aggregation was retarded by both aspirin and indomethacin. This divergent effect of cyclooxygenase inhibitors in different vascular beds may depend on the relative importance of prostacyclin in the different beds or on the capacity of cyclooxygenase inhibitors to influence this prostacyclin production in different beds. Caution is urged before acceptance of a central role for PGI2, however, because of the capability of microvasculatures and adjacent tissue to synthesize a number of other products whose interaction with platelets and with aspirin and indomethacin remains to be elucidated.
D000818:Animals; D001158:Arteries / Q000502:physiology*; D001160:Arterioles / Q000502:physiology*; D001241:Aspirin / Q000494:pharmacology*; D002196:Capillaries / Q000502:physiology; D011464:Epoprostenol / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008643:Mesentery / Q000098:blood supply* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D013268:Stimulation, Chemical
D011464:Epoprostenol; D001241:Aspirin; D007213:Indomethacin