Endothelin receptor alterations in equine airway hyperreactivity

Area of Science:

• Veterinary Medicine
• Pulmonary Physiology
• Pharmacology

Background:

• Summer pasture-associated obstructive pulmonary disease (SPAOPD) is a common respiratory condition in horses.
• Endothelin-1 (ET-1) is a potent vasoconstrictor and mediator of airway tone.
• The role of ET-1 and its receptors in equine SPAOPD remains incompletely understood.

Purpose of the Study:

• To investigate the involvement of endothelin-1 (ET-1) and its receptors in the airway hyperreactivity observed in horses with SPAOPD.
• To compare the effects of ET-1 and its receptor antagonists on bronchial smooth muscle from healthy and SPAOPD-affected horses.

Main Methods:

• Bronchial rings from healthy and SPAOPD-affected horses were used in organ bath studies.
• The effects of ET-1 and specific ET(A) and ET(B) receptor antagonists (BQ-123 and IRL-1038) on bronchial contraction were assessed.
• Reverse-transcription polymerase chain reaction (RT-PCR) was employed to evaluate ET(B)-receptor gene expression.

Main Results:

• Horses with SPAOPD exhibited significantly greater ET-1-induced bronchial contraction compared to healthy horses.
• ET(A)-receptor blockade enhanced ET-1 responses in healthy horses, while ET(B)-receptor blockade reduced responses in SPAOPD-affected horses.
• SPAOPD-affected horses showed increased ET(B)-receptor affinity and a trend towards increased ET(B)-receptor mRNA expression.

Conclusions:

• Airway hyperreactivity to ET-1 in horses with SPAOPD is partly mediated by the activation of pulmonary ET(B) receptors.
• ET(B) receptors appear to play a more significant role in the airway smooth muscle of SPAOPD-affected horses than in healthy horses.