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Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2006; 70(3); 197-205;

Comparison of 2 endothelin-receptor antagonists on in vitro responses of equine palmar digital arterial and venous rings to endothelin-1.

Abstract: The goals of this study were to determine the concentration-response (C-R) relationship of endothelin-1 (ET-1), compare 2 ET-receptor antagonists and determine the antagonist concentrations that block the vasomotor effects of ET-1, and compare the effectiveness of ET-1 and previously studied vasoconstrictors in equine palmar digital arterial and venous rings in vitro. Vessel rings from 8 nonlaminitic horses were placed in Tyrode's solution, 1 side fixed to the floor of an organ bath and the other side fixed to a force-displacement transducer. Two separate studies were conducted: (I) incubation with a single ET-receptor antagonist (PD142893 or PD145065 at a concentration of 10(-7), 10(-6), or 10(-5) M), followed by determination of an ET-1 C-R curve (using concentrations of 10(-10) to 10(-6) M) for medial vessel rings; and (II) comparison of ET-1 with norepinephrine and histamine (10(-10) to 10(-6) M) and comparison of contractile responses of medial and lateral vessel rings. In study I, ET-1 administration caused pronounced and sustained concentration-dependent contraction of vessel rings; these contractile responses were decreased by 10(-5) M PD142893 and were completely blocked by 10(-5) M PD145065. Venous rings had greater apparent maximum contraction in response to ET-1 than arterial rings. In study II, the relative sensitivity of norepinephrine was found to be equivalent to that of ET-1, whereas that of histamine was lower. No significant differences were observed between responses of medial versus lateral vessel rings. Thus, ET-1 is a potent vasoconstrictor of equine palmar digital arteries and veins, and the ET-receptor antagonist PD145065 is more effective than PD142893 in inhibiting these contractile effects in vitro. (Traduit par Docteur Serge Messier)
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Publication Date: 2006-07-21 PubMed ID: 16850942PubMed Central: PMC1477928
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  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the responses of horse vascular tissue to endothelin-1, a potent vasoconstrictor, and compares the effects of two different types of antagonist drugs on these responses. Endothelin-1 was found to cause intense and prolonged contraction of vascular tissue, which was lessened by the drug PD142893 and completely blocked by the drug PD145065.

Research Objective and Methods

  • The researchers sought to establish the relationship between the concentration of endothelin-1 (ET-1), a potent vasoconstrictor, and its effect on palmar digital arterial and venous rings in horses. They aimed to compare the effectiveness of two ET-receptor antagonists (PD142893 and PD145065) in blocking the vasomotor effects of ET-1.
  • The research involved the use of vessel rings from eight nonlaminitic horses. These were placed in Tyrode’s solution, with one side fixed to an organ bath base and the other attached to a force-displacement transducer. This setup allowed the researchers to monitor and measure the contraction of the vessel rings in response to various substances.

Twin Research Studies

  • In the first part of this study, the research evaluated the effects of a single dose of an ET-receptor antagonist followed by ET-1 on medial vessel rings. Different concentrations of the antagonists (PD142893 or PD145065) were tested. It was observed that ET-1 caused pronounced and long-lasting concentration-dependent contractions of the vessel rings. These contractions were reduced at 10(-5) M concentration of PD142893 and were completely blocked at the same concentration of PD145065.
  • The second part of the study compared the effects of ET-1, norepinephrine, and histamine on medial and lateral vessel rings. It found that the relative sensitivity of norepinephrine was similar to that of ET-1, whereas histamine’s was lower. There were no significant differences observed between the responses of medial versus lateral vessel rings.

Research Findings and Implications

  • The research established that ET-1 is a powerful vasoconstrictor of equine palmar digital arteries and veins. It also determined that the ET-receptor antagonist PD145065 is more effective than PD142893 in blocking these contractile effects in a laboratory setting. The greater apparent maximum contraction responses to ET-1 in venous rings than in arterial rings was another notable finding.
  • The study’s results could potentially inform future research in developing more effective ET-receptor antagonists, which could then be utilized in the management or treatment of diseases related to vascular tissue contraction in horses.

Cite This Article

APA
Stokes AM, Venugopal CS, Hosgood G, Eades SC, Moore RM. (2006). Comparison of 2 endothelin-receptor antagonists on in vitro responses of equine palmar digital arterial and venous rings to endothelin-1. Can J Vet Res, 70(3), 197-205.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 70
Issue: 3
Pages: 197-205

Researcher Affiliations

Stokes, Ashley M
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge 70803-8410, USA. astokes@lsu.edu
Venugopal, Changaram S
    Hosgood, Giselle
      Eades, Susan C
        Moore, Rustin M

          MeSH Terms

          • Animals
          • Arteries / drug effects
          • Arteries / physiology
          • Dose-Response Relationship, Drug
          • Endothelin Receptor Antagonists
          • Endothelin-1 / antagonists & inhibitors
          • Endothelin-1 / pharmacology
          • Horses / physiology
          • In Vitro Techniques
          • Muscle, Smooth, Vascular / drug effects
          • Muscle, Smooth, Vascular / physiology
          • Oligopeptides
          • Toes / blood supply
          • Veins / drug effects
          • Veins / physiology

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          Citations

          This article has been cited 2 times.
          1. 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.
            doi: 10.1007/s00011-014-0736-2pubmed: 24764104google scholar: lookup
          2. Gauff FC, Patan-Zugaj B, Licka TF. Effect of short-term hyperinsulinemia on the localization and expression of endothelin receptors A and B in lamellar tissue of the forelimbs of horses. Am J Vet Res 2014 Apr;75(4):367-74.
            doi: 10.2460/ajvr.75.4.367pubmed: 24669922google scholar: lookup
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