MODULATION OF BRONCHIAL SMOOTH-MUSCLE FUNCTION IN HORSES WITH HEAVES

Four mechanisms that modulate airway smooth muscle function in normal horses were studied in the bronchi of horses affected by the airway ob structive disease heaves. Results were compared with data from histori cal controls studied by the same personnel in the same laboratory. Rin gs from the left cranial lobar bronchus (LB1) and small bronchi (5 mm OD) were suspended in muscle baths, and the isometric tension was meas ured. The inhibitory nonadrenergic noncholinergic (iNANC) function was studied in LB1. After the LB1 segments were pretreated with atropine and contracted with histamine, electrical field stimulation (EFS) indu ced little or no relaxation, indicating iNANC dysfunction in horses wi th heaves. Bronchi from animals with heaves were hyporesponsive to EFS and acetylcholine. Epithelial removal augmented the contractile respo nse of small bronchi to acetylcholine more in animals with heaves than in control animals, indicating an enhanced function of epithelial-der ived relaxing factor. In contrast, cyclooxygenase inhibition with mecl ofenamate (10(-6) M) increased the EFS-induced contraction of small br onchi less in affected horses than in control horses, suggesting a cha nge in prostaglandin production in favor of excitatory prostanoids. We conclude that in the bronchi of horses with heaves the iNANC function is defective, the response of smooth muscle to cholinergic activation is diminished, the production of epithelial-derived relaxing factor i s enhanced, and the inhibitory function of prostanoids is reduced.