Aspirin cyclo-oxygenase inhibitor

Antagonistic effects of cyclo-oxygenase inhibitors (indo-metacin or aspirin) have been repeatedly reported both in hypertension and in heart failure, strongly suggesting that there may be prostaglandin participation in the clinical response to ACE inhibitors (103,104). In animals, although not in all experimental models, aspirin can attenuate the beneficial effects of ACE inhibitors on ventricular remodelling after myocardial infarction. 

Aspirin acts by interfering with the synthesis of prostaglandins, which are connected to the causes of inflammation and fever. In particular it is an inhibitor of the cyclo-oxygenase (Cox-2) enzyme. Studies of the use of aspirin as an anticlotting agent suggest that half an aspirin tablet per day may reduce the risk of heart attack and stroke in some people.3... 

Aspirin irreversibly blocks the production of thromboxane A2 by binding to cyclo-oxygenase (COX-1) in platelets, and so inhibits platelet aggregation. The beneficial cardiovascular effects are attributed to this effect. Other NSAIDs that are COX-1 inhibitors also have this effect, but it is more short-lived since they bind reversibly. These NSAIDs can therefore competitively inhibit the binding of aspirin to platelets (a fact that was shown in vitro as early as the 1980s ). When these NSAIDs are present in sufficient quantities when a daily low-dose of aspirin is given, they therefore reduce its antiplatelet effect. In vitro study confirms that COX-2 selective NSAIDs have less effect. ... 

Whether endogenous prostacyclin modulates platelet activity in vivo is uncertain, but studies using cyclo-oxygenase and thromboxane synthase inhibitors in animal models of thrombosis support this hypothesis. Inhibition of platelet deposition on de-endothelialized rabbit abdominal aorta by aspirin is dose dependent, being less at higher doses at which coincident inhibition... 

Recently, it has been postulated that even using the common inhibitor aspirin it should nonetheless be possible to interfere more or less selectively with the thromboxane biosynthesis by platelets. The inhibition of the vessel wall cyclo-oxygenase was found to be of shorter duration than that in platelets [401,402] this is expected since the nucleated endothelial cells can rapidly synthesize new enzyme. Furthermore, it has been demonstrated that the platelet cyclo-oxygenase is much more sensitive to aspirin, requiring both lower concentration and shorter exposure to the drug for complete inhibition than does the vascular enzyme [403]. 

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