Effect of chronic low dose aspirin on platelet and vascular eicosanoid metabolism in nonhuman primates (Macaca fascicularis).
It has been suggested that inhibition of platelet cyclooxygenase by chronic low dose aspirin may spare vascular prostacyclin production. Conventional doses of aspirin (greater than 5 mg/kg) have been shown to inhibit the generation of both thromboxane A2 and prostacyclin. Low dose aspirin inhibits prostacyclin production by excised human venous tissue, thus questioning the selectivity of such regimens. However, many clinical and surgical conditions requiring platelet inhibition involve the arterial system. We have studied the effects of various aspirin regimens on platelet, venous, and arterial cyclooxygenase activity in a nonhuman primate (Macaca fascicularis). We determined the lowest chronic dose of oral aspirin required to effectively inhibit platelet cyclooxygenase and aggregation to be 1 mg/kg. After 14 days of 0, 1, or 2 mg/kg aspirin, intact veins and arteries were surgically removed and perfused, and luminal prostacyclin (6-keto-PGF1 alpha) generation was assessed. Levels of 6-keto-PGF1 alpha in venous perfusates were reduced by 89% and 86% (p less than 0.05) after 1 and 2 mg/kg, respectively. Arterial 6-keto-PGF1 alpha levels were unchanged by 1 mg/kg aspirin, but after 2 mg/kg were reduced by 66% (p less than 0.05). Preferential inhibition of platelet over arterial cyclooxygenase is thus achievable, but only over a narrow dose range.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008084:Lipoxygenase / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011863:Radioimmunoassay; D013928:Thromboxane A2 / Q000096:biosynthesis
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin