SYNERGISM BETWEEN PGE1-METABOLITES (13,14-DIHYDRO-PROSTAGLANDIN-E1, 15-KETO PROSTAGLANDIN-E1, 15-KETO-13,14-DIHYDRO-PROSTAGLANDIN-E1) AND NITRIC-OXIDE (NO) ON PLATELET-AGGREGATION

A synergistic antiplatelet effect between prostaglandins (PG), cAMP-stimulators and nitric oxide (NO), a cGMP-stimulator, has already been described. Data on a synergism between NO and the metabolites of PGE1, however, are lacking so far. We therefore tested the antiplatelet activity of the metabolites of PGE1 alone and their synergism with NO on human platelets of 8 healthy volunteers in vitro. 13,14-DH-PGE1 (ID 50 = 10.8 ng/ml platelet rich plasma (PRP)) was the only PGE1 metabolite inhibiting the ADP-induced platelet aggregation, its efficacy being 76.4% of the parent compound PGE1 (ID 50 = 8.25 ng/ml PRP). NO (ID 50 = 0.52-mu-M) also inhibited platelet aggregation. The combined addition of 13,14-dihydro-prostaglandin E1 (13,14-DH-PGE1) and NO caused an additive effect. The other PGE1-metabolites tested, 15-keto prostaglandin (15-K-PGE1) (ID 50 = 16.2.-mu-g/ml PRP) and 15-keto-13,14-dihydro-prostaglandin (15-K-13,14-DH-PGE1) (ID 50 = 14.8-mu-g/ml PRP), neither had any relevant antiaggregatory capacity themselves nor a synergistic effect with NO. These findings could be of clinical relevance as a NO-synergism may occur not only with therapeutically administered PGE1 but also with its biologically active metabolite 13,14-DH-PGE1.