Organic nitrates and compounds that increase intraplatelet cyclic guanosine monophosphate (cGMP) levels enhance the antiaggregating effects of the stable prostacyclin analogue 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 cyclic guanosine monophosphate (cGMP) levels on platelet aggregation, release reaction and cyclic nucleotide content: in particular cyclic adenosine monophosphate (cAMP) and cGMP. Iloprost inhibited in a dose-dependent way the platelet aggregation in response to collagen, adenosine diphosphate (ADP) and adrenaline and it increased the intraplatelet cAMP concentrations. GTN directly decreased the platelet responses and increased the intraplatelet levels of both cGMP and cAMP. GTN (20 x 10(-6) mol/l) and L-arginine (0.2 x 10(-3) mol/l) potentiated the inhibitory effects of iloprost on platelet aggregation and release reaction. Our results suggest: 1. A synergistic effect of the simultaneous increase of both cAMP and cGMP on the biochemical steps involved in the inhibition of the platelet response; 2. An influence of cGMP on cAMP accumulation.
Anfossi
G
G
Department of Clinical and Biological Sciences, University of Turin Ospedale S. Luigi Gonzaga, Orbassano Torino, Italy.
Massucco
P
P
Mularoni
E
E
Cavalot
F
F
Mattiello
L
L
Trovati
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D000242:Cyclic AMP / Q000097:blood / Q000502:physiology; D006152:Cyclic GMP / Q000097:blood / Q000502:physiology*; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010978:Platelet Factor 4 / Q000378:metabolism; D015290:Second Messenger Systems / Q000187:drug effects*
D010975:Platelet Aggregation Inhibitors; D010978:Platelet Factor 4; D000244:Adenosine Diphosphate; D003094:Collagen; D001120:Arginine; D000242:Cyclic AMP; D005996:Nitroglycerin; D006152:Cyclic GMP; D016285:Iloprost; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine