ORIGIN AND REGULATION OF VAGAL PREGANGLIONIC NEURON SUBTYPES CONTROLLING AIRWAY SMOOTH MUSCLE TONE

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The primary role of the airways is to allow the exchange of oxygen and carbon dioxide between the environment and the lungs. However, the airways are not merely a series of static tubes, but rather their size (or caliber) is subject to breath-by-breath alterations, thereby regulating gas exchange to match the body's demands. Regulation of airway caliber is achieved largely by subconscious changes in the tone of the muscle lining the airway wall. Airway muscle tone is primarily under the control of the parasympathetic division of the autonomic nervous system. Two distinct types of parasympathetic nerves innervate the airways: One type employs the neurotransmitter acetylcholine which causes airway muscle to contract and the airways to constrict, while the other type employs nitric oxide which evokes airway dilatation. The normal regulation of airway caliber is altered in a variety of inflammatory airways diseases. In asthma and chronic obstructive pulmonary disease (COPD) there is an increase in airway muscle tone (airway constriction) which compromises the normal movement of gasses and contributes to the morbidity and mortality of the diseases. There is a growing body of evidence to suggest that exaggerated airway muscle tone may in part result from dysfunction of either the contractile or relaxant parasympathetic nerves innervating the airways. However, at present very little is known about the parasympathetic pathways regulating airway caliber. A complete understanding of the mechanisms controlling airway smooth muscle tone is therefore essential to fully understanding possible role of autonomic dysfunction in the pathogenesis of obstructive airways diseases. The aim of this grant is to better define the physiological and anatomical properties of airway parasympathetic nerves in the brain stem.