Variations in systemic and pulmonary endothelin-1 in horses with recurrent airway obstruction (heaves)

Recurrent airway obstruction (RAO) is an asthma-like condition of the horse that represents a major cause of morbidity and loss of performance. The exact pathogenesis of asthma in man is unclear but the role of endothelin (ET) is currently under investigation, thus sparking interest in the bronchoconstrictive and vasoconstrictive properties of endothelin in the equine-specific disease entity. In this study, we investigated the levels of ET-1 in systemic blood, as well as in bronchoalveolar lavage (BAL) from horses with RAO. We also studied how these values might correlate with those of lung function tests and pulmonary artery pressure. Five horses with RAO were evaluated both in remission and in crisis and compared to five control horses. RAO horses had significantly (P<0.05) higher systemic ET-1 levels than control horses. They also had a negative arteriovenous ET-1 difference that may correspond to a net uptake of ET-1 in the lung. RAO horses in crisis had increased amounts of immunoreactive ET in BAL fluid compared to normal control subjects. Additionally, the reduction in lung function seen in RAO horses in crisis was significantly correlated with lower epithelial lining fluid ET-1 levels. Our results demonstrate that endothelin may contribute to the pathogenesis of asthma.