ORGANIC NITRATES AND COMPOUNDS THAT INCREASE INTRAPLATELET CYCLIC GUANOSINE-MONOPHOSPHATE (CGMP) LEVELS ENHANCE THE ANTIAGGREGATING EFFECTSOF THE STABLE PROSTACYCLIN ANALOG ILOPROST

The present study investigated the effect of a combination between the stable prostacyclin (PGI2) analogue iloprost and compounds, glyceryl trinitrate (GTN) and L-arginine-, which enhance the intraplatelet cycl ic guanosine monophosphate (cGMP) levels on platelet aggregation, rele ase reaction and cyclic nucleotide content: in particular cyclic adeno sine monophosphosphate (cAMP) and cGMP. Iloprost inhibited in a dose-d ependent way the platelet aggregation in response to collagen, adenosi ne diphosphate (ADP) and adrenaline and it increased the intraplatelet cAMP concentrations. GTN directly decreased the platelet responses an d increased the intrapletelet levels of both cGMP and cAMP. GTN (20 x 10(-6) mol/l) and L-arginine (0.2 x 10(-3) mol/1) potentiated the inhi bitory effects of iloprost on platelet aggregation and release reactio n. Our results suggest: 1. A synergistic effect of the simultaneous in crease of both cAMP and cGMP on the biochemical steps involved in the inhibition of the platelet response; 2. An influence of cGMP on cAMP a ccumulation.