Enhanced prostacyclin production by dipyridamole in man

The effects of some phosphodiesterase (PDE) inhibitors (dipyridamole, theophylline, papaverine and SH-869) on prostacyclin (PGI2) production have been studied in vitro and in vivo. PGI2 was bioassayed by Vane's superfusion technique. In rabbit aortic rings, only dipyridamole in concentrations from 1 to 12 microM was able to stimulate PGI2 biosynthesis in a dose-dependent manner. This effect was also detected with so-called "exhausted" rabbit aortic rings. The other PDE inhibitors used, both in microM and mM concentration, did not affect PGI2 biosynthesis. Dipyridamole was found to increase PGI2 production in healthy volunteers, when given both by infusion (8 micrograms/kg/min x 2h) and by oral administration (375 mg/day for seven days). Circulating PGI2 and PGI2 production induced by a 3-min period of ischaemia were increased by an average of 137% (p less than 0.001) and 30.8% (p less than 0.001) respectively. Saline and theophylline (as aminophylline) infusions used as controls did not affect PGI2 production.