The reduction of platelet thrombi on damaged vessel wall by a thromboxane synthetase inhibitor in rabbits.
The role of thromboxane A2 (TXA2) in platelet-vessel wall interaction was investigated using 1-benzylimidazole (1-BI), a selective thromboxane synthetase inhibitor. 1-BI (0.9 mM) will reduce the aggregatory response of rabbit platelets to 0.2 mM arachidonate by 50% and their production of TXA2 by 84%. The effect of 1-BI on platelet thrombus formation was evaluated in vivo on New Zealand white male rabbits using the autologous indium-111 labeled platelet technique. After injection of autologous 111In-platelets, 10 cm of the abdominal aorta was de-endothelialized with a balloon catheter. Three hours later the animals were sacrificed and injured and uninjured segments of the aorta removed. The radioactivity and dry weight of the tissue were determined. The radioactivity/gm of tissue was greater for the injured tissue than for the uninjured tissue. 1-BI at 10 mg/kg reduced the specific platelet accumulation at the injured site (n = 5; 4.8 +/- 0.3 X 10(5) cpm/gm) compared to the controls (n = 10; 11.7 +/- 2.1 X 10(5) cpm/gm). Platelet accumulation on the injured tissue was further reduced by increasing the dosage to 30 mg/kg. Thirty minutes after 1-BI administration (30 mg/kg), platelets were less sensitive to arachidonate-induced aggregation (a 67% decrease) and TXA2 production was decreased 82%. Alterations in platelet sensitivity persisted for up to 3 hours. These findings indicate that TXA2 plays an important role in platelet-vessel wall interaction.
D000818:Animals; D001012:Aorta, Abdominal / Q000033:anatomy & histology / Q000293:injuries / Q000503:physiopathology; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009929:Organ Size; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; C017062:1-benzylimidazole; D013929:Thromboxane B2; D010088:Oxidoreductases; D013930:Thromboxane-A Synthase