Inhibition of platelet activity by S-nitrosoglutathione during coronary angioplasty.
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.
Langford
E J
EJ
King's College School of Medicine and Dentistry, Department of Medicine, London, UK.
Brown
A S
AS
Wainwright
R J
RJ
de Belder
A J
AJ
Thomas
M R
MR
Smith
R E
RE
Radomski
M W
MW
Martin
J F
JF
Moncada
S
S
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
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