The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels.
Abstract: Endotoxin has been implicated in the pathophysiology of acute laminitis. The aim of this study was to examine the direct effects of endotoxin on isolated equine digital blood vessels. Equine digital veins (EDV), incubated in Krebs-Henseleit solution containing lipopolysaccharide (LPS) (1 microg/ml) became hyporesponsive to 5-HT after 16 h. Cycloheximide and ibuprofen blocked this effect of LPS and increased the maximum response obtained to 5-HT when compared to control vessels. L-nitroarginine methyl ester (L-NAME) reversed the hyporesponsiveness caused by LPS. Vessels maintained in culture medium containing LPS also became hyporesponsive to 5-HT, an effect which was completely prevented by ibuprofen but only partially reversed by L-NAME. Measurements were made of 6-keto PGF1alpha and nitrite production by segments of equine digital artery and vein in culture medium alone or co-cultured with peripheral blood leucocytes. LPS did not stimulate nitrite production from vessel segments but increased nitrite release from leucocytes, an effect which was inhibited by cycloheximide and L-NAME. Lipopolysaccharide increased 6-keto PGF1alpha production by blood vessels, an effect which was inhibited by cycloheximide and ibuprofen but not L-NAME. No synergistic effect on release of nitrite or 6-keto PGF1alpha was noted in co-cultures of blood vessels and leucocytes. These data suggest that induction of cyclo-oxygenase by LPS was a major cause of hyporesponsiveness of digital blood vessels to 5-HT. Release of nitric oxide was not detectable in LPS-stimulated blood vessels maintained in culture even in the presence of activated leucocytes yet L-NAME did protect against LPS-induced hyporesponsiveness indicating nitric oxide synthase induction may play some role in the effect of LPS. These findings are important in furthering our understanding of the pathophysiological mechanisms underlying the vascular changes which occur in acute laminitis.
Publication Date: 1999-07-13 PubMed ID: 10402134DOI: 10.1111/j.2042-3306.1999.tb03175.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research aims to decipher the direct impact of endotoxin on equine blood vessels. The findings suggest that the presence of endotoxin can lead to unresponsiveness of equine digital blood vessels, a condition that can be alleviated by specific medications and might play a crucial role in understanding acute laminitis in horses.
Introduction
- The study revolves around identifying the direct effects of endotoxins on isolated equine digital blood vessels.
- Endotoxins have often been linked to the pathophysiology of acute laminitis in horses, a severe disease affecting the hooves.
- Discovering the effects of endotoxins would contribute significantly to grounding a solid understanding of the vascular changes in acute laminitis.
Research Methodology
- The researchers incubated equine digital veins (EDV) in Krebs-Henseleit solution with lipopolysaccharide (LPS), a type of endotoxin, to perceive its effects.
- After 16 hours, the veins became less responsive to 5-HT, a neurotransmitter.
- The study then used cycloheximide and ibuprofen and recorded an increase in maximum response to 5-HT compared to control vessels. Furthermore, L-nitroarginine methyl ester (L-NAME) was used to reverse the LPS-induced hyporesponsiveness.
- They also measured production of 6-keto PGF1alpha and nitrite by segments of equine digital artery and vein in different conditions namely withheld in culture medium only or co-cultured with peripheral blood leucocytes.
- In specific, LPS did escalate nitrite release from leucocytes, but not from vessel segments.
Findings and Implications
- The experiment concluded that cyclo-oxygenase induction by LPS led to hyporesponsiveness of the digital blood vessels to 5-HT.
- Additionally, it was found that nitric oxide, though not detectable in LPS-stimulated blood vessels even in co-presence of activated leucocytes, might have some contribution in LPS effect as its synthase induction could protect against LPS-induced hyporesponsiveness.
- The study’s findings suggest the cardinal role of LPS in developing unresponsiveness in equine digital blood vessels, leading directly to acute laminitis. It also identified the potential inhibitors that can counter this.
- Such insights could contribute significantly to our understanding of the pathophysiological processes underlying the vascular changes in equine acute laminitis and aid in devising efficient treatment strategies in the future.
Cite This Article
APA
Bailey SR, Elliott J.
(1999).
The role of prostanoids and nitric oxide in endotoxin-induced hyporesponsiveness of equine digital blood vessels.
Equine Vet J, 31(3), 212-218.
https://doi.org/10.1111/j.2042-3306.1999.tb03175.x Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, London, UK.
MeSH Terms
- 6-Ketoprostaglandin F1 alpha / biosynthesis
- Acute Disease
- Animals
- Culture Techniques
- Cycloheximide / pharmacology
- Cyclooxygenase Inhibitors / pharmacology
- Enzyme Inhibitors / pharmacology
- Foot Diseases / etiology
- Foot Diseases / physiopathology
- Foot Diseases / veterinary
- Free Radical Scavengers / pharmacology
- Hoof and Claw / blood supply
- Hoof and Claw / drug effects
- Horse Diseases / etiology
- Horse Diseases / physiopathology
- Horses
- Ibuprofen / pharmacology
- Inflammation / veterinary
- Leukocytes / physiology
- Lipopolysaccharides / toxicity
- NG-Nitroarginine Methyl Ester / pharmacology
- Nitric Oxide / physiology
- Nitrites / metabolism
- Prostaglandins / physiology
- Protein Synthesis Inhibitors / pharmacology
- Serotonin / pharmacology
- Vasoconstriction / drug effects
- Veins / drug effects
- Veins / physiopathology
Citations
This article has been cited 2 times.- Morgan RA, Keen JA, Walker BR, Hadoke PW. Vascular Dysfunction in Horses with Endocrinopathic Laminitis.. PLoS One 2016;11(9):e0163815.
- Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J. The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro.. Inflamm Res 2014 Aug;63(8):637-47.
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