Airways neural control and airways hyperresponsiveness in the ferret.

The objectives of these studies were to characterize: (1) neural control of the ferret airways and (2) mechanisms that induce airways hyperresponsiveness after ozone(O{dollar}\\sb3{dollar}) inhalation. In the ferret airways, contractions are produced by cholinergic neurons, and acetylcholine (ACh), methacholine (MCh) and carbachol (CCh) induce concentration-dependent contractions. The order of potency for contraction of the trachea and bronchi is CCh {dollar}\\ge{dollar} MCh {dollar}\u3e{dollar} ACh, and their potency is dependent upon their resistance to degradation by acetylcholinesterase (AChE). Electrical field stimulation (EFS)-elicited contractions are greater in the trachea than the bronchi except in the presence of neostigmine at high frequencies implying that the bronchi have greater activity than the trachea. Regional differences in AChE activity also exist within the trachea. The potency of ACh to contract the middle trachea is greater than in the distal trachea, however, no difference in potency exists if neostigmine is used to inhibit AChE in the middle and distal tracheas. Propranolol can completely abolish relaxation in the trachea, but propranolol and L-NAME is required to completely inhibit neurally-mediated relaxation in the bronchi. This suggests that the ferret trachea predominantly relaxes by sympathetic neural mechanisms and the bronchi has an additional NO neural relaxation mechanism. O{dollar}\\sb3{dollar} induces airways hyperresponsiveness in the ferret and significantly increases the sensitivity of the airways to inhaled MCh in vivo. Alterations in neural control produce greater contractions by increasing the concentration of ACh at the airways smooth muscle. Decreased activity of the AChE after ozone exposure increases the local concentration of ACh at the smooth muscle and thus increases contractions. O{dollar}\\sb3{dollar} also affects the inhibitory Nonadrenergic-noncholinergic (i-NANC) control of the airways. O{dollar}\\sb3{dollar}-induces increases in NO production which was demonstrated by an increase in the propranolol-insensitive relaxations of the bronchi. These results would imply that alterations in both the parasympathetic and i-NANC nervous systems are involved in airways hyperresponsivness. In conclusion, the ferret provides a good model for neural control of airways smooth muscle. The airways have both excitatory and inhibitory neural mechanisms and alterations of these neural controls can lead to airways hyperresponsiveness