A popular, though somewhat disputed hypothesis is that patients with allergic asthma and certain other respiratory tract diseases that are characterized by hyperresponsive airways, exhibit exaggerated adverse bronchomotor responses primarily becasue of some anomaly in the parasympathetic reflex control of airway caliber. The nature of the neural mechanisms mediating these abnormal reflexes has not be elaborated. The overall goal of this project is to identify the anomaly within the parasympathetic nervous system that could lead to airway hyperreactivity. Successful identification could result in the development of a more enlightened treatment of patients with this specific problem than is currently available. In order to achieve this goal studies will be done in both anesthetized and unanesthetized dogs in whom reflex changes in bronchomotor tone can be easily monitored. Reportedly, the prevailing state of oxygenation can dramatically affect the magnitude of reflex bronchomotor responses. Hypoxia potentiates and hyperoxia attenuates the magnitude of such responses. This suggests that carotid body chemoreceptors could be involved in mediating the effects. In order to determine their impact upon these reflexes, the reflexes will be tested before and after removal of carotid bodies in both acute studies as well as unanesthetized but trained dogs. In addition neural recordings will be made from these receptors in anesthetized dogs. A quantitative evaluation will be made of the relationship between chemoreceptor activity and the magnitude of the reflex bronchomotor response. A similar comparison will be done between baroreceptor activity and reflex bronchomotor responses. In addition the effects of carotid body resection upon the bronchomotor reflexes of natively allergic and other dogs whose airways have been made hyperresponsive by ozone exposure will be studied. One other site which may participate in modifying the magnitude of bronchomotor reflexes in the central nervous system. Studies in anesthetized dogs relating phrenic nerve discharge to reflex alterations in bronchomotor tone will be done in an effort to determine whether a control system exists which can alter bronchomotor reflexes independently of ventilatory responses. These data will provide unique information about the interactions that occur among the different components making up the reflex bronchomotor pathways. This may lead to defining the anomalies in these reflexes that could cause hyperreactive airways.
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