Effects Of Pentoxifylline, Penbutolol, Prenylamine, Clofibric Acid And Nicotinic Acid On The Release Of Prostacyclin-(PGI2-) Like Activity From Rat Aorta In Vivo And In Vitro
Aortas from rats, treated with 5-20 mg/kg of pentoxifylline (pof), penbutolol, prenylamine, clofibric acid or nicotinic acid showed, ex vivo, a significantly higher release of acid labile PGI2-like anti-aggregatory activity compared to controls. This activity could be suppressed by pre-treatment with 2 mg/kg Indomethacin. When incubated with rat aortas in vitro, pof showed a similar stimulatory effect on PGI2-like release, whereas clofibric-and nicotinic acid had no significant effect in this system. Pof and all other drugs mentioned above in therapeutical concentrations had virtually no effect on induced aggregation of human platelets in vitro. However, in the presence of small amounts PGI2 in vitro, inhibition of aggregation and platelet cyclic AMP are enhanced synergistically above the effects of PGI2 and pof individually.We conclude from these experiments that therapeutic doses of all drugs in our study stimulate in vivo the release of PGI2-like activity from vessel walls, thus inhibiting platelet aggregation in vivo. The primary site of action of pof seems to be the vessel wall, whereas the effect of clofibric acid and nicotinic acid on the vessel walls seem to be secondary. The elevation of platelet cyclic AMP levels which generally parallels PGI2-induced inhibition of aggregation might be further enhanced by pof known as an inhibitor of platelet cyclic AMP phosphodiesterase, thus explaining the observed synergistic effects between PGI2 and pof.