CONTROL OF AIRWAY CALIBER DURING EXERCISE

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.)
Although human airways are known to dilate during exercise, the neural
mechanisms causing this increase in airway caliber have not yet been
defined. The first aim of this application is to determine the sources
from which these bronchodilating mechanisms arise. The three candidates
to be investigated are a reflex arising from contracting hindlimb
muscle, central command whose locus is believed to be the subthalamic
locomotor region, and the Hering-Breuer reflex, which arises from the
stimulation of slowly adapting receptors in the lungs. The second aim
is to develop an understanding about the central site of integration and
the final common pathway causing the exercise-induced increases in
airway caliber. An important candidate for the site of integration is
the caudal ventrolateral medulla, an area which is just dorsal to the
lateral reticular nucleus. Likewise, an important candidate for the
site of the final common pathway is the vagal motor nucleus, the nucleus
ambiguous. A dog model will be used to test the following hypotheses:
1) that activation of cells within the subthalamic locomotor region
decreases both total lung resistance and transverse tension from the
trachealis muscle by withdrawing cholinergic input to airway smooth
muscle; 2) that activation of cells within the ventral tegmental field
of the pons, which evokes extensor muscle tone, increase the magnitude
of the bronchodilation evoked by activation of the subthalamic locomotor
region; 3) that blockade of excitatory amino acid receptors in the
caudal ventrolateral medulla prevents the decreases in total lung
resistance and tracheal smooth muscle tension arising from the hindlimb
muscle reflex, from the Hering-Breuer reflex and from the subthalamic
locomotor region (i.e., central command); 4) that the cells of origin
for the vagal preganglionic fibers, whose inhibition causes
bronchodilation, can be located electrophysiologically in the external
portion of the nucleus ambiguus; 5) that the impulse activity of these
vagal preganglionic cells is inhibited by contraction of hindlimb muscle,
by inflation of the lungs and by activation of cells in the subthalamic
locomotor region; and 6) that blockade of excitatory amino acid
receptors in the caudal ventrolateral medulla prevents the inhibition
of vagal preganglionic bronchomotor cells by hindlimb muscle contraction,
by lung inflation and by activation of cells in the subthalamic
locomotor region.
StatusFinished
Effective start/end date12/31/896/30/98

Funding

  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute
  • National Heart, Lung, and Blood Institute

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