Acetylsalicylic acid (aspirin) inhibits prostanoid synthesis by irreversible acetylation of fatty acid cyclooxygenase (EC 1.14.99.1). It thereby inhibits synthesis of pro-aggregatory thromboxane A2 (TXA2) by platelets and is widely used in the treatment and prophylaxis of vascular disease. Its efficacy, however, may be reduced since it also inhibits formation of prostacyclin (PGI2) which is a vasodilator and anti-aggregatory agent. There is uncertainty over the optimum dose regimen for aspirin since although it inhibits platelet thromboxane production for many days, the magnitude and duration of its effect on PGI2 production by vascular endothelium in vivo is unknown. Resting plasma concentrations of PGI2 (measured as the stable hydrolysis product 6-oxo-PGF1 alpha) are at or below the limit of sensitivity of the most sensitive assays and cannot therefore be used to demonstrate a reduction in production. Bradykinin stimulates PGI2 synthesis by cultured human vascular endothelial cells and we have shown that it stimulates PGI2 production by man in vivo. We report here that an oral dose of aspirin (600 mg) causes rapid and substantial inhibition of bradykinin-stimulated PGI2 production, but recovery occurs within 6 hours; this implies that endothelial PGI2 synthesis would be spared most of the time during dosing once daily with even this relatively large dose of aspirin.
1 Bradykinin, angiotensin II, arginine vasopressin (AVP) or des-amino-D-arginine vasopressin (DDAVP) were administered by intravenous infusion to 10 healthy men.2 The concentration of 6-oxo-prostaglandin Fic, (6-oxo-PGF,,), the stable hydrolysis product of prostacyclin (PGI2), was measured in plasma using gas chromatography/negative ion chemical ionisation mass spectrometry.3 Dose-related increases in plasma concentrations of 6-oxo-PGF,a occurred during administration of bradykinin (100-3200 ng kg -' min '). The concentrations of 6-oxo-PGF,. rose from baseline values in the range < 1.0-4.9 pg ml-' to 24.9-47.6 pg ml-' at maximum tolerated infusion rates.4 There were no changes in the concentrations of 6-oxo-PGFIr during administration of angiotensin II, AVP or DDAVP at infusion rates which caused haemodynamic changes.
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