Effect of various agents on prostaglandin biosynthesis and the anti-aggregatory effect.
In view of the supposed importance of prostacyclin (PGI2) and thromboxane A2 (TXA2) in coronary regulation and platelet aggregation, the hypothesis has been proposed that anti-anginal drugs might increase the blood supply to the heart not only by vasodilation and diminution of cardiac work but also by inhibition of formation of dissolution of platelet aggregates. Anti-anginal drugs. especially dipyridamole and nitroglycerin were investigated to establish whether they increase the biosynthesis or anti-platelet effect of PGI2 and inhibit TXA2 synthesis. In various in vitro models, dipyridamole showed an enhancement of PGI2 synthetase and cyclo-oxygenase activity and increased PGI2 release, whereas it had only a weak inhibiting effect on TXA2 synthesis. There was a stimulating effect on PGI2 formation by some other anti-anginal drugs. in contrast, nitroglycerin did not stimulate the biosynthesis of PGI2 in rabbits or guinea pigs, but strongly inhibited TXA2 formation in platelets. It showed an additional inhibiting effect on platelet aggregation and increased additively or more than additively the anti-platelet effect of small doses of PGI2 in ADP-induced platelet aggregation. A hypothesis is discussed in which the action of nitroglycerin could be brought about by a vasodilating effect, as well as by its anti-platelet action on reversible platelet aggregates.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005748:Gastric Fundus / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006801:Humans; D005996:Nitroglycerin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D013917:Thrombin / Q000502:physiology; D013928:Thromboxane A2 / Q000096:biosynthesis; D014665:Vasodilator Agents / Q000494:pharmacology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D014665:Vasodilator Agents; D013928:Thromboxane A2; D004176:Dipyridamole; D011464:Epoprostenol; D013917:Thrombin; D005996:Nitroglycerin