Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses.
Abstract: To evaluate the roles of 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF) in endotoxin-induced digital hypoperfusion in horses. Methods: 6 healthy adult Thoroughbreds. Methods: Horses were treated with IV administration of saline (0.9% NaCl) solution (control treatment) or the 5-HT 1B/D selective antagonist, GR55562 (0.3 mg/kg), prior to tryptamine infusion (1.6 microg/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 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: 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.
Publication Date: 2008-02-05 PubMed ID: 18241016DOI: 10.2460/ajvr.69.2.199Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The abstract of the research article discusses a study that aimed to investigate the roles of certain substances, specifically 5-hydroxytryptamine (5-HT), thromboxane A2 (TxA2), and platelet-activating factor (PAF), in causing restricted blood flow in horses’ extremities due to the effects of endotoxins.
Research Methodology
- The study was conducted on six healthy adult Thoroughbred horses.
- These horses were treated with various substances and their reactions were measured. These substances included an IV administration of saline solution as a control; GR55562, an antagonist of 5-HT 1B/D; aspirin, an anti-inflammatory drug; and WEB2086, a PAF antagonist. These drugs were sometimes used in combination.
- The method of measuring the reactions included Doppler ultrasonography to measure blood flow in the horses’ digits, temperature measurements of the hoof wall and coronary band surface, and blood samples to determine plasma 5-HT and TxA2 concentrations.
Results and Conclusions
- The antagonist GR55562 effectively eliminated the restricted blood flow in the horses’ digits that was caused by the infusion of tryptamine (a byproduct of 5-HT).
- Neither the PAF antagonist WEB2086 nor GR55562 had any effect on the changes in digit perfusion or plasma mediator concentrations caused by the infusion of lipopolysaccharide (LPS), a type of endotoxin.
- Aspirin significantly reduced the increase in TxA2 concentration and digit hypoperfusion caused by LPS, whether it was administered two hours or four days in advance. It also demonstrated greater effects in reducing LPS-induced hypothermia when combined with GR55562.
- Based on these findings, the researchers concluded that TxA2 and 5-HT play significant roles in mediating LPS-induced digit hypoperfusion in horses. Meanwhile, PAF does not seem to have a role in the release of 5-HT or TxA2 or in the hypoperfusion.
Cite This Article
APA
Menzies-Gow NJ, Sepulveda MF, Bailey SR, Cunningham FM, Elliott J.
(2008).
Roles of thromboxane A2 and 5-hydroxytryptamine in endotoxin-induced digital vasoconstriction in horses.
Am J Vet Res, 69(2), 199-207.
https://doi.org/10.2460/ajvr.69.2.199 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, Royal Veterinary College, Hatfield, Hertfordshire AL9 7TA, England.
MeSH Terms
- Animals
- Aspirin / pharmacology
- Azepines / pharmacology
- Benzamides / pharmacology
- Blood Platelets / drug effects
- Calcimycin / pharmacology
- Female
- Horses
- Leukocytes / drug effects
- Leukocytes / metabolism
- Lipopolysaccharides / toxicity
- Male
- Platelet Activating Factor / metabolism
- Platelet Membrane Glycoproteins / antagonists & inhibitors
- Pyridines / pharmacology
- Receptors, G-Protein-Coupled / antagonists & inhibitors
- Serotonin / metabolism
- Thromboxane A2 / metabolism
- Time Factors
- Triazoles / pharmacology
- Tryptamines / pharmacology
- Vasoconstriction / drug effects
- Vasoconstriction / physiology
Citations
This article has been cited 1 times.- Brooks AC, Menzies-Gow N, Bailey SR, Cunningham FM, Elliott J. Endotoxin-induced HIF-1alpha stabilisation in equine endothelial cells: synergistic action with hypoxia. Inflamm Res 2010 Sep;59(9):689-98.
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