Inhibition of human blood platelet aggregation and the stimulation of nitric oxide synthesis by aspirin.
Incubation of platelet-rich plasma with 80 microM aspirin that resulted in the inhibition of both the secondary phase of ADP induced platelet aggregation and prostaglandin synthesis simultaneously stimulated the production of NO in platelets. Furthermore it was found that the treatment of platelet-rich plasma either with 80 microM ibuprofen or salicylic acid, like aspirin, which inhibited the secondary phase of platelet aggregation by ADP and prostaglandin synthesis, also stimulated the production of NO in the absence of added ADP. However the inhibition of prostaglandin synthesis by ibuprofen or salicylic acid, unlike aspirin, was transient in nature. Incubation of washed platelets with any of these three compounds also stimulated NO synthesis indicating that the effect of these compounds was not mediated through plasma proteins. The in vitro effect of aspirin on the increase of NO in platelets could also be demonstrated by in vivo exposure of platelets to the compound. It was concluded that either a temporary or a lasting inhibition of prostaglandin synthesis by these inhibitors resulted in the synthesis of NO in resting platelets. Since NO is a potent inhibitor of platelet aggregation the inhibition of platelet aggregation, by these compounds may not be the consequence of the inhibition of prostaglandin synthesis alone, but could also be related, at least partly, to the stimulated synthesis of NO by these inhibitors.
Chakraborty
Kushal
K
Sinha Institute of Medical Science and Technology, Calcutta, India.
Khan
Gausal Azam
GA
Banerjee
Pratik
P
Ray
Udayan
U
Sinha
Asru K
AK
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D020156:Salicylic Acid / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D008315:Malondialdehyde; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D006152:Cyclic GMP; D020156:Salicylic Acid; D001241:Aspirin; D007052:Ibuprofen