Exogenous nitric oxide inhibits platelet activation in whole blood.
We examined the effect of NO on collagen-induced whole blood aggregation and platelet activation in whole blood by using impedance aggregometry and flow cytometry. For the extracellular generation of NO, we chose sodium nitroprusside dihydrate (SNP), and as intracellular generators of NO, L-arginine and isosorbide dinitrate (ISDN). The latter two significantly inhibited whole blood aggregation, whereas SNP had no such effect. The inhibitory effect of ISDN was diminished by addition of methylene blue (MB) or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl 3-oxide (carboxyl-PTIO), and the inhibitory effect of L-arginine was diminished by addition of N(G)-monomethyl-L-arginine monoacetate (L-NMMA). Although the addition of ISDN increased the cyclic guanosine monophosphate (cGMP) level in whole blood and in the suspension of platelets and white blood cells (PLTs + WBCs), no increase was found in platelet-rich plasma (PRP). The P-selectin expression on the platelet surface in whole blood was reduced by ISDN and L-arginine. These findings suggest that the intracellular generation of NO inhibits whole blood aggregation, and this mechanism may play an important role in its antithrombotic effect in whole blood.
Yoshimoto
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H
Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Suehiro
A
A
Kakishita
E
E
D001120:Arginine / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen; D006152:Cyclic GMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014914:Whole Blood Coagulation Time
D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D003094:Collagen; D001120:Arginine; D006152:Cyclic GMP; D007548:Isosorbide Dinitrate