Endothelin receptor alterations in equine airway hyperreactivity

• Published in: Canadian journal of veterinary research 2006, Vol.70 (1), p.50-57
• Main Authors: Venugopal, C.S, Polikepahad, S, Holmes, E.P, Heuvel, J.V, Leas, T.L, Moore, R.M
• Format: Article
• Language: English
• Subjects: Animals; bronchi; 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; muscle contraction; Organ Culture Techniques - veterinary; Poaceae; Receptors, Endothelin - metabolism; respiratory tract diseases; Reverse Transcriptase Polymerase Chain Reaction - veterinary; Seasons
• ISSN: 0830-9000

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.