The differential inhibition of prostaglandin synthesis in platelets and vascular tissue in response to aspirin.
Since aspirin inhibits the platelet as well as vascular prostaglandin synthesis it may therefore, paradoxically induce a thrombotic tendency when used as an antithrombotic agent. The in vivo effect of therapeutic doses of aspirin on the prostaglandin synthetic capacity of the rat platelets and vascular tissue was therefore studied to determine the significance of this paradoxical aspirin effect. A single aspirin dose of 5 mg/kg or greater was found to significantly decrease the synthesis of prostaglandin E by rat platelets. Even the normal augmentation of PGE synthesis by N-ethyl maleimide was significantly reduced by this single aspirin dose. In contrast, doses as high as 20 mg/kg of aspirin failed to reduce the production of 6-keto PGF1 alpha by aortic slices from rats pretreated with aspirin. These results indicate that the cyclo-oxygenase enzyme (CO) system in the prostaglandin biosynthetic pathway within blood vessel walls has the capacity to recover from this inhibitory effect of aspirin or it is less susceptible to inhibition than the CO in platelets. This relative resistance of CO to the inhibitory effects of aspirin may serve to protect the organism from excessive thrombotic tendencies brought about by the effect of aspirin on the vascular prostaglandin generating system. These results indicate that an aspirin dose of 5-10 mg/kg would be optimal if aspirin were to be used as an antithrombotic agent.
D015121:6-Ketoprostaglandin F1 alpha; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D005033:Ethylmaleimide / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011460:Prostaglandins F / Q000378:metabolism; D051381:Rats
D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D015121:6-Ketoprostaglandin F1 alpha; D011451:Prostaglandin-Endoperoxide Synthases; D005033:Ethylmaleimide; D001241:Aspirin