Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses

Abstract

Objective - To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF) in endotoxin-induced digital hypoperfusion in horses. Animals - 6 healthy adult Thoroughbreds. Procedures - Horses were treated with IV administration of saline (0.9% NaCl) solution (control treatment) or the 5-HT1B/D selective antagonist, GR55562 (0.3 mg/kg), prior to tryptamine infusion (1.6 μg/ kg/min or 30 minutes) to establish an effective GR55562 dose. In a crossover study, horses were treated with IV administration of saline solution (control treatment), aspirin (4 mg/kg, 2 hours or 4 days before lipopolysaccharide [LPS] infusion), GR55562 (0.3 mg/kg), the PAF antagonist WEB2086 (3 mg/kg), or aspirin plus GR55562 prior to LPS infusion (30 ng/kg for 30 minutes). Digital blood flow was measured by use of Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures were made. Serial blood samples were collected and plasma 5-HT and TxA2 concentrations determined. Results - GR55562 abolished tryptamine-induced digital hypoperfusion. Neither WEB2086 nor GR55562 affected LPS-induced alterations in digital perfusion or plasma mediator concentrations. Aspirin given 2 hours before LPS administration abolished the increase in plasma TxA2 concentration and significantly attenuated LPS-induced digital hypoperfusion. Aspirin given 4 days before LPS significantly attenuated the increase in plasma TxA2 concentration and digital hypothermia. Aspirin plus GR55562 had a greater effect on LPS-induced digital hypothermia than aspirin alone. Conclusions and Clinical Relevance - Thromboxane A2 and 5-HT played a role in mediating LPS-induced digital hypoperfusion in horses. Platelet-activating factor appeared unimportant in mediating LPS-induced 5-HT or TxA2 release or digital hypoperfusion.