Effects of furosemide, exercise, and atropine on tracheal mucus transport rate (TMTR) in horses were investigated. Atropine (0.02 mg/kg of body weight) administered IV or by aerosolization significantly (P < 0.05) decreased TMTR at 60, but not at 30 minutes after its administration in standing horses. Furosemide (1.0 mg/kg, IV) did not have any significant effect on TMTR when measured at 2 or 4 hours after its administration in standing horses. Exercise alone or furosemide (1.0 mg/kg, IV) administration followed 4 hours later by exercise did not alter TMTR, compared with values for standing control or exercised horses administered saline solution. Atropine (0.02 mg/kg, IV) administered after exercise significantly (P < 0.05) decreased TMTR, compared with values for no exercise standing controls, for exercise after administration of saline solution, and for furosemide and exercise.

During acute bouts of recurrent airway obstruction (heaves) in horses, neutrophils that are capable of increased production of reactive oxygen species accumulate in the airways. In the study reported here, the effect of hydrogen peroxide (H2O2; 1 micromolar to 0.1M), one of these reactive oxygen species products, on the responses of isolated trachealis muscle of horses was determined. Before and after incubation with H2O2, contractile responses to acetylcholine, electrical field stimulation (EFS), 127 mM KCl, and relaxation responses to isoproterenol and activation of the nonadrenergic noncholinergic inhibitory response (iNANC) were evaluated. Beginning at 1 mM, H2O2 contracted trachealis muscle in a concentration-dependent manner. This contraction was unaffected by atropine (1 micromolar), tetrodotoxin (1 micromolar), or 1 micromolar meclofenamate. Contraction of trachealis muscle in response to H2O2 is, therefore, not attributable to release of prostaglandins, acetylcholine, or other neurotransmitters. Above a concentration of 0.1 mM, H2O2 depressed the responses to EFS. acetylcholine, and KCl in a concentration-dependent manner. At 0.1M, H2O2 decreased the maximal responses to EFS, acetylcholine, and KCl by 62.7 +/- 7.2, 60.58 +/- 6.12, and 37.8 +/- 9.54%, respectively. In the presence of meclofenamate (1 micromolar), partial but significant protection against 1 to 100 mM H2O2 was observed. In tracheal strips contracted with 0.3 micromolar methacholine, H2O2 had no effect on the isoproterenol concentration-response curve. Up to a concentration of 100 mM, H2O2 had no effect on iNANC response. However, in the presence of 100 mM H2O2, this response was abolished in 2 of 4 horses. We conclude that high concentrations of H2O2 affected the responses of airway smooth muscle by actions on neurotransmission, muscarinic receptors, and downstream from receptors; some of the H2O2 effects were in part mediated by cyclooxygenase products; and H2O2 had no effect on beta-adrenergic- or iNANC-induced relaxation.

Effects of furosemide, exercise, and atropine on tracheal mucus transport rate (TMTR) in horses were investigated. Atropine (0.02 mg/kg of body weight) administered IV or by aerosolization significantly (P < 0.05) decreased TMTR at 60, but not at 30 minutes after its administration in standing horses. Furosemide (1.0 mg/kg, IV) did not have any significant effect on TMTR when measured at 2 or 4 hours after its administration in standing horses. Exercise alone or furosemide (1.0 mg/kg, IV) administration followed 4 hours later by exercise did not alter TMTR, compared with values for standing control or exercised horses administered saline solution. Atropine (0.02 mg/kg, IV) administered after exercise significantly (P < 0.05) decreased TMTR, compared with values for no exercise standing controls, for exercise after administration of saline solution, and for furosemide and exercise.

Effects of alpha 2-adrenergic receptor stimulation on the cholinergic contractile response of bovine tracheal smooth muscle were studied. To determine the presence and function of alpha 2-adrenergic receptors on cholinergic nerves innervating bovine tracheal muscle, effects of 2 alpha 2-adrenoceptor agonists and an antagonist were determined. Muscular contractions were elicited by either electrical field stimulation (EFS) or exogenous acetylcholine (ACH). The contractile response to EFS and exogenous ACH was examined for each tissue. Electrical field stimulation of bovine tracheal smooth muscle caused contractions that were completely abolished by atropine, indicating the predominant excitatory innervation of bovine trachea is cholinergic. The alpha 2-adrenoceptor agonists clonidine and medetomidine (10(-6)M to 10(-4)M) concentration-dependently inhibited the contractile response to EFS but not the response to exogenous ACH. Contractions induced by EFS were significantly (P < 0.05) inhibited in clonidine (10(-4) M)-treated tissues at low frequencies (0.1 to 10 Hz), whereas medetomidine (10(-5)M, 10(-4)M) inhibited contractions at all frequencies (0.1 to 30 Hz). Inhibitory effects of the alpha 2-adrenoceptor agonists clonidine and medetomidine were attenuated by the alpha 2-adrenoceptor antagonist tolazoline. The alpha 2-agonists used in this study appear to cause prejunctional inhibition of cholinergic nerves, because the smooth muscle contractions elicited by EFS, but not exogenous ACH, were inhibited, compared with controls.