Influence of SIN-1 on Platelet Ca²⁺ Handling in Patients with Suspected Coronary Artery Disease: Ex Vivo and In Vitro Studies

Summary

The 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and superoxide anion (O₂−). It elicits dose-dependent vasodilation in vivo, in spite of the opposite effects of its breakdown products on vascular tone and platelet aggregation.

This study was designed to investigate the influence of intravenous SIN-1 injection on platelet Ca²⁺ handling in patients undergoing coronary angiography. SIN-1 administration reduced cytosolic [Ca²⁺] in unstimulated platelets by decreasing Ca²⁺ influx. It attenuated Ca²⁺ mobilization from internal stores evoked by thrombin or thapsigargin.

In vitro studies were used as an approach to investigate how simultaneous productions of NO and O₂− from SIN-1 modify thrombin- or thapsigargin-induced platelet Ca²⁺ mobilization. Superoxide dismutase, the O₂− scavenger, enhanced the capacity of SIN-1 to inhibit Ca²⁺ mobilization but catalase had no effect.

This suggests that the effects of SIN-1 on platelet Ca²⁺ handling resemble those of NO, but are modulated by simultaneous O₂− release, independently of H₂O₂ formation.

Keywords

SIN-1 - nitric oxide - superoxide anion - platelet [Ca²⁺]_i - coronary artery disease

• Refrences

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