title: Differential inhibitory effects of isosorbide dinitrate and its mononitrate metabolites on platelet aggregation and thromboxane formation.
abstract: The effects of isosorbide dinitrate (ISDN) and its 2- and 5-mononitrate metabolites (2-ISMN and 5-ISMN) against platelet aggregation and thromboxane release were investigated by analysis of platelet aggregation curves. ISDN, 2-ISMN and 5-ISMN (isosorbide nitrates, ISN) inhibited both ADP- and epinephrine (EPI)-induced platelet aggregation. ISN affected specifically the extent of ADP-induced aggregation and the velocity of EPI-induced effects. 2-ISMN was more potent against platelet aggregation compared to ISDN and 5-ISMN. The isosorbide nitrates were poor inhibitors of both arachidonic acid-induced aggregation and platelet TxB2 release. The differential inhibition by the three isosorbide nitrates of endogenous TxB2 release during ADP-induced aggregation further indicates that 2-ISMN is a significantly more potent platelet inhibitor than either ISDN or 5-ISMN. These studies suggest a role of the metabolites in modulating the pharmacological effects of ISDN on platelet activity.
authors.affiliation: Département de Pharmacologie Cellulaire, Inserm Sc 16, Faculté de Pharmacie, Marseille.
authors.forename: P H
authors.initials: PH
authors.lastname: Rolland
authors.forename: J
authors.initials: J
authors.lastname: Sampol
authors.forename: B
authors.initials: B
authors.lastname: Lacarelle
authors.forename: D
authors.initials: D
authors.lastname: Arnoux
authors.forename: F
authors.initials: F
authors.lastname: Leca
authors.forename: E
authors.initials: E
authors.lastname: Gueydon
authors.forename: J P
authors.initials: JP
authors.lastname: Cano