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

Menzies-Gow, N J and Sepulveda, M F and Bailey, S R and Cunningham, F M and Elliott, J (2008) Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses. AMERICAN JOURNAL OF VETERINARY RESEARCH, 69 (2). pp. 199-207.

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Abstract

Objective-To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A(2) (TxA(2) 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 mu g/kg/min for 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 lipopolysaccharicle [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 TxA(2) concentration and significantly attenuated LPS-induced digital hypoperfusion. Aspirin given 4 days before LPS significantly attenuated the increase in plasma TxA(2) concentration and digital hypothermia. Aspirin plus GR55562 had a greater effect on L PS-induced digital hypothermia than aspirin alone. Conclusions and Clinical Relevance-Thromboxane A(2) and 5-HT played a role in mediating LPS-induced digital hypoperfusion in horses. Plate let-activating factor appeared unimportant in mediating LPS-induced 5-HT or TxA(2) release or digital hypoperfusion.