Assessment of endothelium-dependent vasodilation in equine digital resistance vessels.
Abstract: Haemodynamic disturbances leading to ischaemia and reperfusion injury of the digit are thought to be involved in the pathophysiology of acute equine laminitis. Identification of physiological regulators of blood flow through the equine digit is important in identifying factors, which may predispose animals to laminitis. A method was developed to assess endothelium-dependent responses of the isolated Krebs-perfused equine digit by co-administration of 5-hydroxytryptamine (5-HT) with vasodilator agents, carbachol (CCh), bradykinin (BK) and substance P (SP). Bolus co-administration of CCh (0.02-2 micromol), BK and SP (0.02-0.2 nmol), caused inhibition of the 5-HT pressor response by 50-60%. The vasodilator responses were abolished by the detergent, CHAPS, indicating endothelium dependency; whereas vasoconstrictor responses to 5-HT were potentiated. CCh-induced relaxation was significantly reduced by the nitric oxide synthase inhibitor L-NAME (79.7 +/- 3.4% inhibition), whereas a large proportion of BK and SP-induced relaxation remained (34.1 +/- 6.3% and 33.6 +/- 5.3% inhibition). L-NAME potentiated vasoconstrictor responses to 5-HT. In conclusion, this study demonstrates that endothelium-derived NO modulates the response to vasoconstrictors such as 5-HT and is likely to be an important regulator of blood flow in the digital resistance vascular bed. Other factor(s) released by the endothelium are also important in regulating blood flow, whose identity remains to be established.
Publication Date: 2006-09-09 PubMed ID: 16958783DOI: 10.1111/j.1365-2885.2006.00779.xGoogle Scholar: Lookup
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- Journal Article
Summary
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This research paper presents a study on blood flow regulators in horse digits, which are important in understanding factors that could make horses susceptible to laminitis. The researchers developed a method to assess how these regulators react to various substances, revealing the importance of the endothelium-derived nitric oxide (NO) in controlling vasoconstrictors’ effect and indicating the existence of unspecified factors that also regulate blood flow.
Research Objective
- The study aims to understand the physiological regulators that control the blood flow in horse digits. This is crucial in identifying factors that may predispose animals to laminitis, a painful condition in the hoof of horses usually characterized by ischaemia (restricted blood flow) and reperfusion injury (damages that occur when the blood supply returns after a period of ischaemia).
Methodology
- The researchers developed a method to assess responses by the endothelium, a layer in the blood vessels, of an isolated horse digit when subjected to various substances, including carbachol, bradykinin, and substance P. The horse digit was artificially perfused with a solution known as Krebs solution and co-administered with 5-hydroxytryptamine (5-HT), a neurotransmitter also known as serotonin.
- The study observed the effect of different doses of these substances on the pressor response, a mechanism that raises blood pressure, induced by 5-HT.
Results and Findings
- The co-administration of the vasodilator agents resulted in a 50-60% reduction in the pressor response caused by 5-HT.
- The observed vasodilatory responses were abolished by the application of CHAPS, a molecular biology detergent, indicating that these responses were endothelium-dependent.
- Vasoconstrictor responses to 5-HT were shown to increase following the use of CHAPS.
- The researchers found that the presence of a nitric oxide synthase inhibitor (L-NAME) greatly reduced the relaxation induced by carbachol, suggesting the crucial role of nitric oxide produced by the endothelium in controlling the pressor response.
- In contrast, a large proportion of relaxation induced by bradykinin and substance P remained even with L-NAME, indicating the existence of other factors, separate from nitric oxide, also play a role in blood flow regulation.
Conclusion
- The study concludes that endothelium-derived nitric oxide is a key regulator of blood flow in horse digits by modulating the response to vasoconstrictors such as 5-HT.
- The research also suggests that there are other yet unidentified factors released by the endothelium that play a significant role in regulating blood flow.
Cite This Article
APA
Berhane Y, Elliott J, Bailey SR.
(2006).
Assessment of endothelium-dependent vasodilation in equine digital resistance vessels.
J Vet Pharmacol Ther, 29(5), 387-395.
https://doi.org/10.1111/j.1365-2885.2006.00779.x Publication
Researcher Affiliations
- Department of Veterinary Basic Sciences, Royal Veterinary College, Royal College Street, London, UK.
MeSH Terms
- Animals
- Cholic Acids / pharmacology
- Detergents / pharmacology
- Drug Interactions
- Female
- Hindlimb / blood supply
- Hindlimb / drug effects
- Hindlimb / pathology
- Horses
- Male
- Muscle, Smooth, Vascular / drug effects
- Serotonin / pharmacology
- Serotonin Antagonists / pharmacology
- Vasodilation / drug effects
- Vasodilator Agents / pharmacology
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.
- Gauff F, Patan-Zugaj B, Licka TF. Hyperinsulinaemia increases vascular resistance and endothelin-1 expression in the equine digit.. Equine Vet J 2013 Sep;45(5):613-8.
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