In Vivo Inhibition Of Thromboxane A2-Synthetase : Protective Effect Against Collagen And Arachidonate Infusion
Year: 1981
Type: conference-paper
Abstract: Rabbits and rats anaesthetised with thiopental were infused intravenously either with sodium arachidonate or collagen. Blood pressure and pneumogram were recorded and Thromboxane B2 (T×B2) plasma level was measured prior and after infusion. The aggregating agents elicited hypotension, respiratory break down and killed the animals. These events were associated with an increase in plasma T×B2 concentration. Intraperitoneal pretreatment of animals with derivatives of imidazole (1 -(3-hydroxy-1-oct enyl)-imidazole , chlorhydrat e (CBS6l2) and its nicotinic ester (CBS634) delayed toxic effects and death. In the standard conditions used in this study, the lethal dose of arachidonate in the rabbit was 8.4 t 1.0 mg/kg. This dose was increased to 21.6 ± 4.3 and 50.4 ± 8.0 when the animals were pretreated with CBS6l2 at the dose of respectively 12.5 mg/kg and 25 mg/kg. In the same way, the lethal dose of collagen in the rat was 0.5 ± 0.1 mg/kg in controls and 1.2 t 0.1 mg/kg after treatment with thromboxane-synthetase inhibitor (CBS634 = 25 mg/kg). The lethal dose of collagen was correlated to the concentration of T×B2 formed in the blood (controls : 4.4 ± 0.3 ; treated : 1.7 ± 0.2 ng/ml). Potential interest of these antithrombotic drugs could be strengthened by further pharmacokinetic studies after oral treatment actually in progress.
Source: Thrombosis and Haemostasis
Authors: D Sincholle, C Fontaine, B Martin, C Bonne, P Regnault
Institution: Inserm
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2884341541