Abstract
S-Nitroso-cysteine (SNC), a putative endothelium-derived relaxing factor, potently inhibited collagen- and arachidonic acid-induced platelet aggregation (IC50=100 nM) and thromboxane A2 (TxA2) synthesis of human blood platelets. ODQ, a selective inhibitor of the soluble guanylyl cyclase, inhibited SNC-induced formation of cGMP but did not reverse inhibition by SNC of collagen- and arachidonic acid-induced platelet aggregation. Combination of ODQ with SQ-29548, a specific platelet TxA2 receptor antagonist, did not modify the antiaggregatory action of SNC. Our study shows that SNC inhibits platelet aggregation by cGMP-independent mechanisms that may involve inhibition of TxA2 synthesis in human platelets.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Arachidonic Acid / pharmacology
-
Aspirin / pharmacology
-
Blood Platelets / metabolism*
-
Bridged Bicyclo Compounds, Heterocyclic
-
Collagen / pharmacology
-
Cyclic GMP / metabolism*
-
Cysteine / analogs & derivatives*
-
Cysteine / metabolism
-
Cysteine / pharmacology
-
Fatty Acids, Unsaturated
-
Glutathione / analogs & derivatives
-
Glutathione / metabolism
-
Guanylate Cyclase / antagonists & inhibitors
-
Humans
-
Hydrazines / pharmacology
-
Inhibitory Concentration 50
-
Nitric Oxide / metabolism
-
Nitrites / metabolism
-
Nitroprusside / pharmacology
-
Nitroso Compounds / metabolism
-
Nitroso Compounds / pharmacology*
-
Oxadiazoles / pharmacology
-
Platelet Aggregation / drug effects*
-
Platelet Aggregation Inhibitors / metabolism
-
Platelet Aggregation Inhibitors / pharmacology*
-
Quinoxalines / pharmacology
-
S-Nitrosoglutathione
-
S-Nitrosothiols*
-
Thromboxane A2 / biosynthesis*
Substances
-
1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
-
Bridged Bicyclo Compounds, Heterocyclic
-
Fatty Acids, Unsaturated
-
Hydrazines
-
Nitrites
-
Nitroso Compounds
-
Oxadiazoles
-
Platelet Aggregation Inhibitors
-
Quinoxalines
-
S-Nitrosothiols
-
Nitroprusside
-
Arachidonic Acid
-
Nitric Oxide
-
S-Nitrosoglutathione
-
Thromboxane A2
-
SQ 29548
-
Collagen
-
S-nitrosocysteine
-
Guanylate Cyclase
-
Glutathione
-
Cyclic GMP
-
Cysteine
-
Aspirin