Slow intravenous administration of low dose aspirin inhibits both vascular and platelet cyclooxygenase activity: an experimental study in the rat.
Aspirin irreversibly inhibits cyclooxygenase, thus preventing thromboxane (Tx)A2 production in platelets and prostacyclin in vascular cells. While it is generally accepted that the inhibitory effect of low dose aspirin is cumulative on platelet cyclooxygenase, it is still a matter of debate whether a similar phenomenon also occurs on vascular cyclooxygenase. We have measured in anesthetized rats the inhibitory effect of two doses of aspirin (2.5 and 5.0 mg/kg), given intravenously either as a bolus or as a continuous infusion (for 30 min), on platelet TxB2 and 6-ketoprostaglandin F1 alpha generation by different vascular segments. Aspirin significantly inhibited both platelet and vascular cyclooxygenase independently of the rate of drug administration. The aspirin peak plasma levels at the end of bolus injection was about 170 times higher than the average level measured during the slow infusion (1.21 +/- 0.15 micrograms/ml). At this concentration aspirin did not affect in vitro either platelet or vascular cyclooxygenase activity. Thus the inhibitory effect of aspirin on both platelet and vascular cyclooxygenase seems to be related to total exposure of the enzyme to the drug rather than to the maximal drug concentration attainable in the systemic circulation. These findings may be relevant to the current debate on optimal conditions for the biochemical selectivity of aspirin as an antithrombotic drug.
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage* / Q000097:blood; D001792:Blood Platelets / Q000201:enzymology*; D001808:Blood Vessels / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D011464:Epoprostenol / Q000096:biosynthesis; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D013928:Thromboxane A2 / Q000096:biosynthesis
D016861:Cyclooxygenase Inhibitors; D013928:Thromboxane A2; D011464:Epoprostenol; D001241:Aspirin