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 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.
Le Quan Sang
K H
KH
Pharmacologie, CNRS UMR 8604, Faculté de Médecine Necker-Enfants Malades, Université René Descartes, Paris, France. lequan@necker.fr
Le Feuvre
C
C
Brunet
A
A
Pham
T D
TD
Metzger
J P
JP
Vacheron
A
A
Devynck
M A
MA
D000787:Angina Pectoris / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology; D017023:Coronary Angiography; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors; D013481:Superoxides; C002385:linsidomine; D019284:Thapsigargin; D008981:Molsidomine; D002374:Catalase; D013482:Superoxide Dismutase; D013917:Thrombin; D001241:Aspirin; D002118:Calcium