[Isosorbide dinitrate inhibits in vitro platelet aggregation at submicromolar concentrations]

Area of Science:

• Pharmacology
• Cardiovascular Research

Context:

• Nitrate derivatives, including isosorbide dinitrate (ISDN), are known for vasodilatory effects and in vitro/in vivo platelet anti-aggregant properties.
• The mechanism involves increased intracytoplasmic cyclic GMP (cGMP) concentrations.
• Previous studies on ISDN's anti-platelet activity reported conflicting results regarding effective concentrations and inhibited pathways.

Purpose:

• To investigate the in vitro platelet anti-aggregant activity of ISDN at low doses.
• To determine if ISDN's anti-platelet effect is selective, specifically examining aggregation induced by adenosine diphosphate (ADP).
• To explore the potential potentiation of ISDN's effects by cyclic nucleotide phosphodiesterase inhibitors and agents mimicking adenylate cyclase activity.

Summary:

• ISDN demonstrated in vitro platelet anti-aggregant activity at concentrations around 10^-7 M.
• The anti-aggregant effect was observed against both ADP-induced and platelet-activating factor-acether (PAF-acether)-induced aggregation, indicating a non-selective action.
• Quercetin, a flavonoid, was the only cyclic nucleotide modulator tested that potentiated ISDN's anti-platelet effects.

Impact:

• Provides evidence for ISDN's potent anti-platelet activity at clinically relevant low concentrations.
• Clarifies that ISDN's anti-aggregant effects are not limited to specific agonists like ADP.
• Identifies quercetin as a potential potentiator of ISDN's anti-platelet effects, suggesting novel therapeutic combinations.