title: Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty.
abstract: Platelet activation is associated with acute vessel occlusion and chronic restenosis after percutaneous transluminal coronary angioplasty (PTCA). Organic nitrates, which act by releasing the vasodilator and anti-platelet agent nitric oxide (NO), have a predominantly vasodilator action and cause hypotension at doses required to inhibit platelet activation. S-nitrosoglutathione (GSNO) is an NO donor with a preferential action on platelets. We investigated platelet activation in patients undergoing PTCA and the effect of GSNO. Blood was sampled from the coronary sinus to measure platelet surface expression of P-selectin and glycoprotein IIb/IIIa as indices of platelet activation. In 7 control patients, PTCA caused a rise in platelet surface expression of P-selectin and glycoprotein IIb/IIIa, which was maximal 5 minutes after PTCA, indicating increased platelet activation despite treatment with aspirin, glyceryl trinitrate, and heparin. 6 patients received an intracoronary infusion of GSNO, starting 10 min before PTCA. GSNO significantly inhibited the PTCA-induced increase in platelet surface expression of P-selectin and glycoprotein IIb/IIIa without altering blood pressure. These findings show that platelets are activated following PTCA and that GSNO can prevent this activation.
authors.affiliation: King's College School of Medicine and Dentistry, Department of Medicine, London, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Langford
authors.forename: A S
authors.initials: AS
authors.lastname: Brown
authors.forename: R J
authors.initials: RJ
authors.lastname: Wainwright
authors.forename: A J
authors.initials: AJ
authors.lastname: de Belder
authors.forename: M R
authors.initials: MR
authors.lastname: Thomas
authors.forename: R E
authors.initials: RE
authors.lastname: Smith
authors.forename: M W
authors.initials: MW
authors.lastname: Radomski
authors.forename: J F
authors.initials: JF
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Moncada
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001241:Aspirin / Q000494:pharmacology; D003327:Coronary Disease / Q000517:prevention & control; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D019007:P-Selectin; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D012008:Recurrence; D026422:S-Nitrosoglutathione
chemical_list: D009603:Nitroso Compounds; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D026422:S-Nitrosoglutathione; D006493:Heparin; D005996:Nitroglycerin; D005978:Glutathione; D001241:Aspirin