Endotoxin-induced airway hyperresponsiveness in rabbits: contribution of neuropeptides.

Endotoxin (ET) contaminated dusts frequently can be found in the environment. Especially in agriculture, ETs represent one of the main factors in the development of respiratory diseases. In order to investigate the pathomechanisms of ET induced lung injury, the contribution of the NANC-system of vagal C-fibres to increased airway responsiveness (AR) to cholinergic agents was investigated in anesthetized rabbits. In two control groups of 6 anesthetized Wight New Zealand rabbits each, E. coli ET was infused i.v. (0.4µg/kg) (Group 1) or the aerosolized ET was inhaled for 10 min (Group 2). Before and 1 and 3 hours after ET exposure, AR to 0.2 und 2.0% acetylcholine aerosol was measured. The increased AR after ET application was compared with the ET responses in rabbits with neuropeptides depleted by subchronic capsaicin treatment on four consecutive days (Groups 3 and 4). ET-inhalation and ET-infusion both resulted in a significant increase in AR to ACH (P<0.005). The increase in dynamic elastance (Edyn), as a measure of airway resistance to 0.2% ACH after ET in both groups was comparable with the response to 2.0% ACH before exposure. In rabbits with capsaicin treatment, basal ACH-responsiveness was similar to the control group. After ET-Exposure, increase in AR to ACH was significantly (P<0.05) smaller compared with untreated rabbits. In conclusion, depletion of neuropeptides by capsaicin resulted in a significantly decreased ET-induced airway hyperresponsiveness (AHR) in rabbits, indicating the contribution of the NANCsystem and their neuromodulators to ET -induced AHR. The results confirm the important role of the NANC-system environmental and occupational agents inducedAHR in rabbits.