Prostacyclin reduced

Alt E, Beilharz C, Preter G, et al. Biodegradable stent coating with polylactic acid, hirudin and prostacyclin reduces restenosis [abstr], J Am Coll Cardiol 1997 29 238A. 

COX-2 synthesises PGI2 (prostacyclin) and the high incidence of myocardial infarctions with selective COX-2 inhibitors has been attributed to inhibition of COX-2 in vascular tissues. Prostacyclin, made by blood vessel walls, inhibits aggregation of platelets and maintains a balance with thromboxane. Thromboxane, which is released by platelets, promotes clotting. Prostacyclin is synthesised mostly by COX-1, but in humans selective COX-2 inhibition reduces its biosynthesis in vivo. This reduced synthesis may lead to an overactive thromboxane system and increased risk of thromboembolism. 

Aspirin is maximally effective as an antithrombotic agent at the comparatively low dose of 81 to 325 mg per day. (The antipyretic dose of aspirin in adults is 325 to 650 mg every 4 h.) Higher doses of aspirin are actually contraindicated in patients prone to thromboembolism. At higher doses, aspirin also reduces synthesis of prostacyclin, another arachidonic acid metabolite. Prostacyclin normally inhibits platelet aggregation. The prophylactic administration of low-dose aspirin has been shown to increase survival following myocardial infarction, decrease incidence of stroke, and assist in maintenance of patency of coronary bypass grafts. 

BAY 41-2272 is a novel non-NO-based soluble GC activator. It produced a marked inhibition of platelet aggregation in washed platelets and PRP, however, with much lower potency in PRP. Both NO and prostacyclin exhibited synergistic activity with BAY 41-2272 to inhibit platelet aggregation. In vivo, BAY 41-2272 significantly reduced blood pressure in rats, but it had only a small effect on FeCl3-induced thrombosis [107]. 

Peripheral vascular diseases Infusion or intraarterial injection of prostacyclin (PGI ) improves potency of blood vessels in certain peripheral vascular diseases. Infusion of PGI can also reduce the infarct size in immediate postmyocardial infarction period. 

Ea-Kim, L., Javellaud, J., Oudart, N., 1992b. Endothelium-dependent relaxation of rabbit middle cerebral artery to a histamine H3-agonist is reduced by inhibitors of nitric oxide and prostacyclin synthesis. Br. J. Pharmcol. 105, 103-106. 

Prostaglandins Prostaglandins and the other eicosanoids (prostacyclins, thromboxanes and leukotrienes) are derived from arachidonate. These compounds all act as local hormones. Aspirin reduces inflammation by inhibiting prostaglandin synthase, the enzyme that catalyzes the first step in prostaglandin synthesis. 

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