Stimulation of prostacyclin biosynthesis as a possible mechanism of action of dipyridamole
Mentz, P.; Pönicke, K.; Block, H.U.; Giessler, C.; Blass, K.E.; Bayer, B.L.; Förster, W.
Arzneimittel-Forschung 31(12): 2075-2082
1981
ISSN/ISBN: 0004-4172 PMID: 7037009 Document Number: 173064
In microsomes of pig aorta, isolated perfused hearts of guinea-pigs, rabbit vessel preparations and homogenates of rat lungs 2,6-bis-[bis-(beta-hydroxyethyl)-amino]-4,8-dipiper-idino-pyrimido-[5,4-d]pyrimidine (dipyridamole) application caused a marked stimulation of prostacyclin biosynthesis. The oxygen incorporation into arachidonic acid indicating cyclooxygenase and lipoxydase activity under the influence of lyophilised ram vesicle microsomes was increased by dipyridamole. The formation of malondialdehyde and thromboxane A2 in platelet rich plasma of rabbits remained uninfluenced. On the other side the formation of thromboxane A2 was moderately inhibited in homogenates of guinea-pig lungs. The arachidonic acid-induced thrombus formation and following death of rabbits remained uninfluenced. The results indicate that dipyridamole causes a relatively specific alteration of the prostaglandin metabolism stimulating the biosynthesis of prostacyclin but without effect or only moderate inhibition of the formation of thromboxane A2. These effects could be looked upon as an important mechanism for the cardiovascular action of the drug.