title: Studies on inhibition of human platelet function by sodium nitroprusside. Kinetic evaluation of the effect on aggregation and cyclic nucleotide content.
abstract: In this study, we explored the ability of sodium nitroprusside to inhibit the aggregation of human platelets in platelet-rich plasma (PRP) and whole blood and its effects on intracellular levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). The experiments investigated dose-dependent effects of nitroprusside starting from concentrations in the range of circulating levels achievable in vivo during drug administration in humans. Furthermore, we investigated the time-course of both antiaggregating action and the influence on cyclic nucleotide synthesis. Results showed that sodium nitroprusside inhibited the aggregation induced by adenosine 5-diphosphate (ADP) and collagen starting from concentration as low as 2 micromol/l. The IC(50) value for ADP-induced aggregation in PRP was 18.7+/-2.4 micromol/l. The inhibition of platelet aggregation showed a time-dependent behaviour and was not reversible within 90 min. The accumulation of intraplatelet cGMP in the presence of sodium nitroprusside exhibited a comparable time-course characterized by an early increase, a steady state and a late further increase. The time-course of cAMP synthesis was very similar to that of cGMP. Our data evidenced a long-lasting inhibition of platelet responses by sodium nitroprusside and excluded a desensitization of platelet guanylyl cyclase after 3-h exposure to nitric oxide (NO). Furthermore, they indicated a role of cAMP accumulation in the antiaggregating effects of nitroso donor: the simultaneous increase of intracellular content of cAMP and cGMP can synergize in the reduction of the platelet responses.
authors.affiliation: Diabetes Unit, Department of Clinical and Biological Sciences, University of Turin, Azienda Ospedaliera S. Luigi, I-10043 Orbassano, Turin, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Anfossi
authors.forename: I
authors.initials: I
authors.lastname: Russo
authors.forename: P
authors.initials: P
authors.lastname: Massucco
authors.forename: L
authors.initials: L
authors.lastname: Mattiello
authors.forename: A
authors.initials: A
authors.lastname: Balbo
authors.forename: F
authors.initials: F
authors.lastname: Cavalot
authors.forename: M
authors.initials: M
authors.lastname: Trovati
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D009599:Nitroprusside; D000244:Adenosine Diphosphate; D000242:Cyclic AMP; D006152:Cyclic GMP