S-nitroso-glutathione inhibits platelet activation in vitro and in vivo.
1. The effect of S-nitroso-glutathione (GSNO), a stable nitrosothiol, on platelet activation was examined in vitro and in vivo. 2. The adhesion of human platelets to fibrillar collagen and human endothelial cell monolayers was inhibited by GSNO. 3. GSNO caused a concentration-dependent inhibition of collagen-induced platelet aggregation in vitro and decreased ADP-induced aggregation in the conscious rat. 4. Inhibition of platelet aggregation in vitro correlated with the increase in intraplatelet cyclic GMP levels. 5. The release of NO from GSNO was enhanced by platelet lysate, native glutathione and ascorbate. 6. The results show that GSNO is a carrier of NO and therefore has pharmacological activity as an inhibitor of platelet activation.
Radomski
M W
MW
Wellcome Research Laboratories, Beckenham, Kent.
Rees
D D
DD
Dutra
A
A
Moncada
S
S
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000378:metabolism / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D026422:S-Nitrosoglutathione
D007202:Indicators and Reagents; D009603:Nitroso Compounds; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen; D000242:Cyclic AMP; D005978:Glutathione; D006152:Cyclic GMP