Recovery of prostacyclin synthesis by rabbit aortic endothelium and other tissues after inhibition by aspirin.
The effect of aspirin on prostacyclin (PGI2) and thromboxane B2 (TXB2) synthesis was studied in rabbits. Tissues were removed from animals killed at intervals after injection of aspirin, and incubated with Hanks' solution. PGI2 synthesis was monitored by radioimmunoassay of its hydrolysis product, 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha). TXB2 production in clotted blood, also measured by radioimmunoassay, was determined as an index of platelet cyclo-oxygenase activity. 6-oxo-PGF1 alpha and TXB2 production 0.5 h after aspirin were similarly inhibited to less than 5% of control in all incubations. Subsequent recovery of PGI2 synthesis occurred more rapidly in aortic endothelium than in other tissues, including aorta denuded of endothelium. Recovery of TXB2 production was slower than that of PGI2. Intravenous cycloheximide prevented the partial recovery of PGI2 synthesis that otherwise occurred 6 h after aspirin, while intravenous epidermal growth factor increased recovery. It is concluded that in the rabbit, cyclo-oxygenase is synthesized more rapidly in aortic endothelium than in deep layers of aorta, or in the other tissues studied.
Frazer
C E
CE
Ritter
J M
JM
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001241:Aspirin / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003864:Depression, Chemical; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D004815:Epidermal Growth Factor; D003513:Cycloheximide; D011464:Epoprostenol; D001241:Aspirin