Effects of S-nitroso-glutathione in the human forearm circulation: evidence for selective inhibition of platelet activation.
OBJECTIVE
Nitric oxide (NO) is a vasodilator and inhibitor of platelet function. The clinical use of NO donors as inhibitors of platelet activation is limited by their concomitant hypotensive effect. S-nitroso-glutathione (GSNO) has a significant antiplatelet effect at doses that cause only a small decrease in blood pressure in rats. The aim of this study was to examine the antiplatelet and vasodilator properties of this nitrosothiol in the human forearm.


METHODS
Forearm blood flow was measured by forearm occlusion plethysmography in five healthy males. Ex vivo platelet aggregation to ADP was performed in a platelet ionised calcium lumi-aggregometer.


RESULTS
Intra-arterial infusion of GSNO (0.2, 1, and 5 nmol.min-1) resulted in inhibition of ADP (1-10 microM) induced platelet aggregation. This inhibition was submaximal for 0.2 and maximal for 1 and 5 nmol.min-1. However, the antiaggregatory effect observed at the lowest dose of GSNO was accompanied only by a threshold increase in forearm blood flow.


CONCLUSIONS
These results show that GSNO is more effective as an inhibitor of platelet activation than as a vasodilator, suggesting that it is possible to achieve selective antiplatelet and potentially antithrombotic effects with NO donors.
Department of Cardiology, King's College Hospital, Denmark Hill, London, United Kingdom.
A J
AJ
de Belder
R
R
MacAllister
M W
MW
Radomski
S
S
Moncada
P J
PJ
Vallance
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005542:Forearm / Q000098:blood supply*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009603:Nitroso Compounds / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010991:Plethysmography; D012039:Regional Blood Flow / Q000187:drug effects; D026422:S-Nitrosoglutathione; D014664:Vasodilation / Q000187:drug effects
D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D026422:S-Nitrosoglutathione; D000244:Adenosine Diphosphate; D005978:Glutathione