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Home / Equine Research Bank / Can J Vet Res / Endothelin receptor alterations in equine airway hyperreacti...
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2006; 70(1); 50-57;

Endothelin receptor alterations in equine airway hyperreactivity.

Abstract: The purpose of this study was to evaluate the role of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity of horses with obstructive pulmonary disease associated with summer pasture (SPAOPD). The right diaphragmatic lobe of the lung of 8 clinically healthy (unaffected) and 8 SPAOPD-affected horses was collected immediately after euthanasia. Bronchial rings (4 mm wide) were prepared and mounted in organ baths and attached to force transducers interfaced with a polygraph. Four rings were used to study each ET-1 receptor; 1 ring served as the control, and the other 3 were incubated with 10(-9), 10(-7), or 10(-5) M of either BQ-123, an ET(A)-receptor antagonist, or IRL-1038, an ET(B)-receptor antagonist. Cumulative concentrations (10(-8.5) to 10(-6) M) of ET-1 were applied to all rings. Using pooled pulmonary tissue from different regions of the lung, we performed a reverse-transcription polymerase chain reaction (RT-PCR) to determine ET(B)-receptor gene expression. Although ET-1 caused concentration-dependent bronchial ring contraction in both groups of horses, the rings of SPAOPD-affected horses had significantly greater contraction than the rings of unaffected horses. Whereas ET(A)-receptor blockade significantly increased the response to ET-1 in unaffected horses, ET(B)-receptor blockade significantly decreased the response in affected horses. The pA2 values showed a nonsignificant decrease in ET(A)-receptor affinity and a significant increase in ET(B)-receptor affinity in affected horses compared with unaffected horses. The ET(B)-receptor mRNA expression of the pooled pulmonary tissue showed a nonsignificant increase in affected horses compared with unaffected horses. The airway hyperreactivity to ET-1 observed in the bronchial rings from the affected horses appears to be due in part to activation of pulmonary ET(B) receptors, which appear to be inactive in unaffected horses.
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Publication Date: 2006-03-22 PubMed ID: 16548332PubMed Central: PMC1325094
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

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.

The research paper investigates the role of the endothelin-1 (ET-1) and its receptors on the airway hyperreactivity of horses suffering from obstructive pulmonary disease. The findings suggest that the activation of pulmonary ET(B) receptors may contribute to the heightened airway reactivity in affected horses.

Overview of Study Design

  • The research was conducted on lung tissues of 8 healthy horses and 8 horses affected by obstructive pulmonary disease associated with summer pasture (SPAOPD).
  • The right diagphragmatic lobe of the lung was collected immediately after euthanasia.
  • Bronchial rings were prepared from the lung tissues and mounted in organ baths. These were attached to force transducers that were interfaced with a polygraph.
  • Different amounts of endothelin-1 (ET-1) receptor antagonists BQ-123 and IRL-1038 were applied to three of the four bronchial rings. The fourth ring served as the control.
  • The researchers measured the contraction of the bronchial rings in response to cumulative concentrations of ET-1.
  • A reverse-transcription polymerase chain reaction (RT-PCR) was used to determine the expression level of ET(B)-receptor in pooled pulmonary tissue from different regions of the lung.

Major Findings

  • Even though ET-1 caused contraction in bronchial rings of both affected and unaffected horses, the contraction was significantly greater in the rings of the affected horses.
  • Inhibition of the ET(A)-receptors led to an increased response to ET-1 in unaffected horses, whereas blocking the ET(B)-receptors significantly reduced the response in affected horses.
  • The pA2 values displayed a nonsignificant reduction in the affinity of ET(A)-receptors and a significant increase in ET(B)-receptor affinity in the horses suffering from obstructive pulmonary disease.
  • The mRNA expression of ET(B)-receptor in the pooled pulmonary tissue was found to be slightly increased in affected horses. However, the difference was not statistically significant.

Conclusions

  • The researchers concluded that the airway hyperreactivity to ET-1 observed in the bronchial rings from the affected horses seems to be, at least partly, caused by the activation of pulmonary ET(B) receptors.
  • This implies that in healthy horses, these receptors are not activated and hence do not contribute to airway hyperreactivity.
  • The findings provide potential therapeutic targets to treat obstructive pulmonary disease in horses, but further studies are needed to fully understand the underlying molecular mechanisms.

Cite This Article

APA
Venugopal CS, Polikepahad S, Holmes EP, Heuvel JV, Leas TL, Moore RM. (2006). Endothelin receptor alterations in equine airway hyperreactivity. Can J Vet Res, 70(1), 50-57.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 0830-9000
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 70
Issue: 1
Pages: 50-57

Researcher Affiliations

Venugopal, Changaram S
  • Equine Health Studies Program, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA. cvenugopal@vetmed.lsu.edu
Polikepahad, Sumanth
    Holmes, Earnestine P
      Heuvel, John Vanden
        Leas, Tara L
          Moore, Rustin M

            MeSH Terms

            • Animals
            • Bronchial Hyperreactivity / metabolism
            • Bronchial Hyperreactivity / physiopathology
            • Bronchial Hyperreactivity / veterinary
            • Dose-Response Relationship, Drug
            • Endothelin-1 / antagonists & inhibitors
            • Endothelin-1 / pharmacology
            • Gene Expression
            • Horse Diseases / metabolism
            • Horse Diseases / physiopathology
            • Horses
            • Lung Diseases, Obstructive / metabolism
            • Lung Diseases, Obstructive / physiopathology
            • Lung Diseases, Obstructive / veterinary
            • Organ Culture Techniques / veterinary
            • Poaceae
            • Receptors, Endothelin / metabolism
            • Reverse Transcriptase Polymerase Chain Reaction / veterinary
            • Seasons

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            Citations

            This article has been cited 2 times.
            1. Venugopal CS, Holmes EP, Polikepahad S, Laborde S, Kearney M, Moore RM. Neurokinin receptors in recurrent airway obstruction: a comparative study of affected and unaffected horses.. Can J Vet Res 2009 Jan;73(1):25-33.
              pubmed: 19337392
            2. Polikepahad S, Haque M, Francis J, Moore RM, Venugopal CS. Characterization of endothelin receptors in the peripheral lung tissues of horses unaffected and affected with recurrent airway obstruction.. Can J Vet Res 2008 Jul;72(4):340-9.
              pubmed: 18783023
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