Heavey, Dennis J., Barrow, Susan E., Hickling, Nicola E., and Ritter, James M.
Nature; November 1985, Vol. 318 Issue: 6042 p186-188, 3p
Acetylsalicyclic acid (aspirin) inhibits prostanoid synthesis1,2by irreversible acetylation of fatty acid cyclooxygenase (EC 220.127.116.11)3. It thereby inhibits synthesis of pro-aggregatory thromboxane A2(TXA2) by platelets2,4and 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)5,6which is a vasodilator and anti-aggregatory agent7,8. There is uncertainty over the optimum dose regimen for aspirin since although it inhibits platelet thromboxane production for many days4, the magnitude and duration of its effect on PGI2production by vascular endothelium in vivo is unknown. Resting plasma concentrations of PGI2(measured as the stable hydrolysis product 6-oxo-PGF1α) are at or below the limit of sensitivity of the most sensitive assays9and cannot therefore be used to demonstrate a reduction in production. Bradykinin stimulates PGI2synthesis by cultured human vascular endothelial cells10and we have shown that it stimulates PGI2production by man in vivo11. We report here that an oral dose of aspirin (600 mg) causes rapid and substantial inhibition of bradykinin-stimulated PGI2production, but recovery occurs within 6 hours; this implies that endothelial PGI2synthesis would be spared most of the time during dosing once daily with even this relatively large dose of aspirin.