Prostacyclin production by rat aorta "in vitro" is increased by the combined action of dipyridamole plus pentoxifylline.
The present study evaluates the effect of dipyridamole and pentoxifylline, individually and in combination, on PGI2-like production and arachidonic acid metabolism of rat aorta "in vitro". Pentoxifylline 100 microM and dipyridamole 92 and 184 microM increased PGI2-like activity, as measured by the platelet aggregation inhibitory capacity of the aortic ring incubates, by 71%, 46% and 60% respectively; a greater increase in PGI2-like activity was observed with the combination of the drugs than when they were used separately. This effect was observed even at the lowest doses assayed. In fact, dipyridamole 9.2 microM plus pentoxifylline 1 microM increased the PGI2-like activity by 30% while the individual increase was 4.5% and 10.6% respectively. To obtain more information on the effect of the dipyridamole-pentoxifylline combination on arachidonic acid metabolism, arteries were incubated with (1-14C) arachidonic acid, and the 6-keto-PGF1 alpha and PGE2 quantified. Dipyridamole 92 microM plus pentoxifylline 1 and 10 microM increased 6-keto-PGF1 alpha and PGE2 production by about 30% and 48% respectively while the combination with pentoxifylline 100 microM increased the 6-keto-PGF1 alpha 76.5% and the PGE2 50%. The possible biological effect and therapeutic implications of increased PGI2 production by the arteries due to the dipyridamole-pentoxifylline combination remains to be ascertained.
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D004176:Dipyridamole / Q000494:pharmacology*; D011464:Epoprostenol / Q000096:biosynthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010431:Pentoxifylline / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013805:Theobromine / Q000031:analogs & derivatives*
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D004176:Dipyridamole; D011464:Epoprostenol; D013805:Theobromine; D010431:Pentoxifylline