Evaluation of plasma 11-dehydro-thromboxane B2 as an indicator for thromboxane A2 synthesis in vivo in laboratory animals.
Since thromboxane (TX) B2 is not a reliable indicator of TXA2 generation in vivo, because of artifactual TXA2 generation during blood collection, we tested the feasibility of replacing TXB2 with 11-dehydro (dh)-TXB2 as the indicator. Plasma levels of TXB2 and 11-dh-TXB2 were measured after i.v. administration of TXB2 to rabbits, guinea pigs, rats, dogs and a monkey, and after i.v. infusion of collagen in rabbits. In the rabbits and dogs, 2,3-dinor-TXB2 levels were also measured. After intravenous injection of TXB2 (10 micrograms/kg) in rabbits, the ratio of the area under the curve (AUC) of 11-dh-TXB2 to that of TXB2 (1.94) was far higher than the AUC ratio between 2,3-dinor-TXB2 and TXB2 (0.42). When endogenous TXA2 was generated by infusion of collagen (2 mg/kg/5 min), the plasma level of 11-dh-TXB2 was significantly increased, and had a longer half-life than TXB2. In the guinea pigs, rats and monkey, the peak plasma levels of 11-dh-TXB2 were significantly increased after injection of TXB2 (10 micrograms/kg, i.v.), whereas the AUC ratios of 11-dh-TXB2/TXB2 were less than one fourth of that in rabbits. No significant increase in 11-dh-TXB2 was observed after TXB2 injection (10 micrograms/kg) in dogs, but the 2,3-dinor-TXB2 level rose significantly, its AUC ratio to TXB2 being 0.29, comparable with that in rabbits. The order of the 11-dh-TXB2/TXB2 AUC ratios was: rabbits > guinea pigs > monkey > rats >> dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Kawamura
M
M
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Harada
Y
Y
Katori
M
M
D000818:Animals; D000830:Animals, Laboratory / Q000097:blood*; D003094:Collagen / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D007262:Infusions, Intravenous; D008252:Macaca fascicularis; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000096:biosynthesis* / Q000097:blood; D013929:Thromboxane B2 / Q000819:agonists / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
D013929:Thromboxane B2; D013928:Thromboxane A2; C028965:2,3-dinor-thromboxane B2; C049235:11-dehydro-thromboxane B2; D003094:Collagen