Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black walnut heartwood extract induced equine laminitis.
Abstract: Inflammation and vascular dysfunction occur concurrently during the prodromal stages of equine laminitis. The aim of this study was to provide insights into the role that thromboxane and isoprostanes may play in the development of black walnut heartwood extract (BWHE)-induced laminitis. Horses were divided into two groups, either control or BWHE-administered horses. Plasma concentrations of thromboxane increased transiently after administration of BWHE and coincided with the nadir in white blood cell counts, whereas plasma concentrations of iso-prostaglandin PGF(2alpha) (iso-PGF(2alpha)) did not change in either group. At 12h (for the control group) or Obel grade 1 laminitis (for the BWHE group) the horses were euthanized and laminar tissue collected. Laminar arteries and veins were used in functional studies with vasoconstrictor substances and tissue samples were used for the determination of laminar iso-PGF(2alpha) concentrations. Laminar tissue concentrations of iso-PGF(2alpha) were significantly greater in BWHE horses when compared to control horses. In parallel studies concentrations of iso-PGF(2alpha) in laminar tissue samples obtained 1.5 and 3h after administration of BWHE were indistinguishable from those for control horses at 3 or 12h after administration of an equal volume of water. Laminar vessel constrictor responses to either a thromboxane mimetic (U46619), iso-prostaglandin PGE(2) (iso-PGE(2)) or iso-PGF(2alpha) were determined using small vessel myographs. In some vessels, the effects of putative prostanoid and thromboxane receptor antagonists, SQ 29,548, SC-19220 and AH 6809, upon contractile responses were determined. In control horses, U46619, iso-PGF(2alpha) and iso-PGE(2) more potently and efficaciously constricted laminar veins when compared to laminar arteries. Responses of laminar veins from BWHE horses to iso-PGE(2) were similar to those of laminar veins from control horses, whereas iso-PGF(2alpha) elicited significantly greater responses in laminar veins from BWHE horses when compared to controls. In contrast, responses to U46619 were smaller in laminar veins isolated from BWHE horses when compared to those in laminar veins from control horses. In the presence of SQ 29,548, iso-PGF(2alpha) elicited a small dilation in laminar veins from control horses, which was not apparent in laminar veins from BWHE horses. These results are consistent with both systemic and local inflammatory events occurring during the prodromal stages of BWHE-induced laminitis. Because laminar veins are sensitive to thromboxane and isoprostanes, these substances may act as conduits between the inflammatory and vascular events occurring in laminitis and may be therapeutic targets for this crippling condition.
Publication Date: 2008-11-07 PubMed ID: 19111354DOI: 10.1016/j.vetimm.2008.11.005Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This study focuses on the role of thromboxane and isoprostanes in the early stage development of horse laminitis induced by black walnut heartwood extract (BWHE). The main findings indicate that these substances may serve as a link between inflammation and vascular dysfunction in laminitis, providing potential therapeutic targets for this condition.
Research Design and Methods
- Horses were divided into two groups – a control group and a group administered with BWHE.
- Thromboxane and iso-prostaglandin PGF(2alpha) concentrations were monitored in plasma, with the latter’s level remaining unchanged in both groups.
- At specified hours post-administration or at the first stage of laminitis, the horses were euthanized and laminar tissue collected.
- Functional studies were conducted using the laminar arteries and veins with vasoconstrictor substances.
- Laminar iso-PGF(2alpha) concentrations were then determined from tissue samples.
- Possibly concurrent studies were conducted to determine the concentration of iso-PGF(2alpha) in laminar tissue samples obtained at specified hours after BWHE administration.
- The effect of prostanoid and thromboxane receptor antagonists was also tested.
Key Findings
- Thromboxane concentration in plasma increased temporarily after BWHE administration, coinciding with the bottoming out of white blood cell counts.
- Laminar tissue concentrations of iso-PGF(2alpha) were significantly higher in the BWHE group as compared to the controls.
- The results from the application of vasoconstrictor substances suggested differential effect on laminar arteries and veins, with laminar veins being more responsive in control horses.
- Iso-PGF(2alpha) triggered significantly greater responses in laminar veins from BWHE-administered horses compared to the controls.
- On the other hand, the response to U46619, a thromboxane, was reduced in laminar veins isolated from the BWHE horses compared to the control group horses.
- Mimetic agents could elicit dilation in control horse laminar veins, which was not apparent in the BWHE group.
Overall Implications
- The results suggest a link between systemic and local inflammatory events during early stages of BWHE-induced laminitis.
- Since laminar veins were found to be sensitive to thromboxane and isoprostanes, these substances could serve as a link between the inflammatory and vascular events prevalent in laminitis.
- Thus, thromboxane and isoprostanes could be potential therapeutic targets for laminitis treatment.
Cite This Article
APA
Noschka E, Moore JN, Peroni JF, Lewis SJ, Morrow JD, Robertson TP.
(2008).
Thromboxane and isoprostanes as inflammatory and vasoactive mediators in black walnut heartwood extract induced equine laminitis.
Vet Immunol Immunopathol, 129(3-4), 200-210.
https://doi.org/10.1016/j.vetimm.2008.11.005 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Virginia Maryland Regional College of Veterinary Medicine Duck Pond Drive, Blacksburg, VA 24071, United States.
MeSH Terms
- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
- Animals
- Arteries / drug effects
- Arteries / physiology
- Dinoprost / analogs & derivatives
- Dinoprost / pharmacology
- Dinoprostone / analogs & derivatives
- Dinoprostone / pharmacology
- Foot Diseases / chemically induced
- Foot Diseases / veterinary
- Hoof and Claw
- Horse Diseases / chemically induced
- Horse Diseases / metabolism
- Horses
- Inflammation / chemically induced
- Inflammation / metabolism
- Inflammation / veterinary
- Isoprostanes / metabolism
- Isoprostanes / pharmacology
- Juglans / chemistry
- Plant Extracts / chemistry
- Plant Extracts / toxicity
- Random Allocation
- Thromboxanes / metabolism
- Tissue Culture Techniques
- Vasoconstriction / drug effects
- Vasoconstriction / physiology
- Veins / drug effects
- Veins / physiology
- Wood / chemistry
Grant Funding
- CA77839 / NCI NIH HHS
- DK48831 / NIDDK NIH HHS
- ES13125 / NIEHS NIH HHS
- GM15431 / NIGMS NIH HHS
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