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...

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Published in:Cardiovascular research 1994-05, Vol.28 (5), p.691-694
Main Authors: Belder, Adam J de, MacAllister, Raymond, Radomski, Marek W, Moncada, Salvador, Vallance, Patrick J T
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - pharmacology
Adult
blood flow
Depression, Chemical
Dose-Response Relationship, Drug
Forearm - blood supply
Glutathione - analogs & derivatives
Glutathione - pharmacology
Humans
Male
Middle Aged
nitric oxide
Nitroso Compounds - pharmacology
Platelet Activation - drug effects
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - pharmacology
platelets
Plethysmography
Regional Blood Flow - drug effects
S-Nitrosoglutathione
Vasodilation - drug effects
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Summary: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 μM) 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. Cardiovascular Research 1994;28:691-694
ISSN:0008-6363
1755-3245
DOI:10.1093/cvr/28.5.691