Differential effect of aspirin on thromboxane and prostaglandin biosynthesis in man.
1. Effects of a single intravenous dose of aspirin (600 mg) on bradykinin-stimulated prostaglandin (PG) and on thromboxane (TX) biosynthesis were determined in nine healthy male volunteers. Plasma concentrations of 6-oxo-PGF1 alpha and 13,14-dihydro-15-oxo-PGF2 alpha were measured in samples obtained during repeated 10 min intravenous infusions of bradykinin before and up to 6 h after the dose of aspirin. TXB2 was measured in serum from blood allowed to clot at 37 degrees C. 2. Aspirin inhibited bradykinin stimulated PG and platelet TX biosynthesis 0.5 h after the dose. Serum TXB2 remained low, whereas PG synthesis recovered within 6 h. 3. Effects of intravenous sodium salicylate (600 mg) were studied identically in eight subjects. Prostanoid biosynthesis was not inhibited. 4. Biosynthesis of prostacyclin and TXA2 under basal conditions was studied in eight subjects by measuring 2,3-dinor-6-oxo-PGF1 alpha and 2,3-dinor-TXB2 in hourly urine samples obtained during and after intravenous infusion of aspirin and, on a separate occasion, of vehicle. 5. Aspirin infusion reduced urinary excretion of both metabolites greater than 90%, but excretion of 2,3-dinor-6-oxo-PGF1 alpha recovered more rapidly than did that of 2,3-dinor-TXB2. 6. We conclude that cyclo-oxygenase is rapidly synthesised in bradykinin-responsive tissues in vivo and that this reflects similarly rapid enzyme biosynthesis in tissues that produce PGI2 under basal conditions.
Ritter
J M
JM
Department of Clinical Pharmacology, Royal Postgraduate Medical School, Hammersmith Hospital, London.
Cockcroft
J R
JR
Doktor
H S
HS
Beacham
J
J
Barrow
S E
SE
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D007267:Injections; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis* / Q000097:blood; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis*
D011453:Prostaglandins; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D001241:Aspirin