Inhibition of human blood platelet aggregation and the stimulation of nitric oxide synthesis by aspirin

Abstract

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.

Restoration by aspirin of impaired plasma maspin level in human breast cancer

“…Although in this study 150 mg aspirin was consumed by the volunteers, as little as 15 mg aspirin ingestion increased the plasma maspin level by 38% in both breast cancer and normal subjects (unpublished) indicating a possible dose related increase of maspin production by the drug in vivo through NO. It should be mentioned here at this concentration of aspirin little or no inhibition of prostaglandin synthesis could be demonstrated [12], indicating that low amounts of aspirin could be used for the optimal production of maspin in breast cancer patients without producing untoward effects which are created due to the systemic inhibition of prostaglandin synthesis. Furthermore, it was also found that the aspirin induced increase of plasma NO or maspin level was related neither positively nor negatively to the stage of the disease or to the statuses of age, marital status and menstrual phases of the participants.…”

“…Although the total amounts of plasma maspin production in breast cancer due to aspirin ingestion was almost half the amount of the protein present in plasma in normal volunteers, the restored amount of plasma level of maspin in breast cancer achieved through aspirin ingestion was 97% of the normal basal level (4.63 nM VS 4.76 nM). Since aspirin is chronically used for many years in the prevention of coronary artery disease [19] with excellent safety records, it is perhaps be concluded that the chronic use of this compound could be safely used for the prevention and/or control of breast cancer through its ability to ''correct'' plasma maspin level through increased systemic NO synthesis, independent of cyclooxgenase [12]. Although in this study 150 mg aspirin was consumed by the volunteers, as little as 15 mg aspirin ingestion increased the plasma maspin level by 38% in both breast cancer and normal subjects (unpublished) indicating a possible dose related increase of maspin production by the drug in vivo through NO.…”

“…This strategy was based on our report that the ingestion of low amounts of aspirin by normal volunteers resulted in increased plasma NO level [12]. Furthermore this effect of aspirin on NO production was found to be independent of the well-known effect of the compound on the inhibition of prostaglandin synthesis.…”

A Case of Very Late Bare-Metal Coronary Stent Thrombosis Two Weeks after Aspirin Discontinuation, Histopathologic Thrombus Findings and Clinical Considerations

“…Undoubtedly, aspirin still remain the most commonly prescribed drug for prevention of atherothrombotic events. This is due not only to its potent inhibition of thromboxane A2 pathways, which is crucial for platelet activation and aggregation, but also for pleiotropic effects [9]. Furthermore, the endothelium normally provides an efficient barrier against the excessive uptake of lipids.…”

Acetyl salicyclic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients

“…(8) This effect of aspirin, resulting in the stimulation of NO synthesis in various cells, has been reported to be independent of the well-known effect of aspirin on the inhibition of prostaglandin synthesis. (9) Breast cancer is well known for its predisposition to metastasize to different parts of the body, even in those patients who have received difference therapies including chemotherapy, radiation and ⁄ or surgery for the localized condition. (10) In breast cancer patients, aspirin (given orally) has been reported to result in the restoration of impaired maspin production to normal ranges through the restoration of impaired insulin-induced NO synthesis to normal levels.…”