Influence of SIN-1 on platelet Ca2+ handling in patients with suspected coronary artery disease: Ex vivo and in vitro studies

The 3-morpholinosydnonimine (SIN-1) generates both nitric oxide (NO) and su peroxide anion (O-2-). It elicits dose-dependent vasodilation in vivo, in s pite 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 i njection on platelet Ca2+ handling in patients undergoing coronary angiogra phy. SIN-1 administration reduced cytosolic [Ca2+] in unstimulated platelet s 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 p roductions of NO and O-2- from SIN-1 modify thrombin- or thapsigargin-induc ed platelet Ca2+ mobilization. Superoxide dismutase, the O-2- scavenger, en hanced 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 O-2- release, independently of H2O2 formation.