Asthma is a disease characterized by airway hyperreactivity and features episodic periods of reversible airway obstruction. Investigation of the role of neural mechanisms in the bronchospastic manifestation of this disease has centered around efferent autonomic nerves, particularly as they pertain to a central nervous system reflex arc. Recently, neuropeptides derived from sensory nerves innervating the airways have been proposed as being important in modulating airway function to the extent of being involved in an 'axon' reflex network. However, virtually all of the evidence for such a reflex is based on studies in non-pulmonary tissues or on studies using non-physiological stimuli. The hypothesis to be examined in the present study is whether pulmonary sensory nerves or efferent nerves play an important role in the local regulation of bronchomotor tone in guinea-pig airways. The specific objectives are (i) to characterize the central nervous system-independent role of afferent (sensory) and efferent nerves in the modulation or mediation of airway smooth muscle tone caused by a variety of bronchocontrictors in isolated guinea-pig airways, (ii) to identify the physiological importance of non-central nervous system-dependent (or local) reflexes relative to central nervous system reflexes in anesthetized guinea pigs, (iii) to elucidate the features of local reflexes including the breadth of local reflex networks and their role in mechanical distension-induced contraction of the airways. It is proposed that afferent and efferent nerves exert modulatory activities independent of the central nervous system to influence the bronchomotor activity of applied agonists. It is envisaged that information about reflex networks in the airways will provide valuable new insights into the way in which airway smooth muscle tone and responsiveness can be regulated by local mechanisms.
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