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 goal of the proposed experiments, therefore, is to characterize the bronchodilator responses arising from the two neural mechanisms likely to function during exercise. The two mechanisms are: a reflex arising from contracting limb muscle, and central command arising from the subthalamic locomotor region. The second goal of the proposed experiments is to develop an understanding about the central neural pathways and integrating mechanisms mediating exercise- induced bronchodilation. The integrating mechanism is proposed to occur in the caudal ventrolateral medulla. The final common pathway to the airways is proposed to be the vagus nerve, whose inhibition by the two mechanisms is likely to cause the bronchodilation occurring during exercise. The proposed experiments will be performed in unanesthetized decerebrate dogs. Measurements of tracheal tension and total lung resistance will be used to characterize the increases in airway caliber in response to activation of central command and the reflex arising from dynamically contracting skeletal muscle. Central command will be activated by both electrical and chemical (i.e., d1- homocysteic acid and picrotoxin) stimulation of the subthalamic locomotor region. The reflex will be activated using """"""""Kao type"""""""" stimulation of the L7-S, ventral roots. The bronchodilator responses to the two maneuvers will be measured before and after electrical and chemical destruction of the caudal ventrolateral medulla. The effects of the reflex and central command on the discharge of cells with vagal preganglionic fibers projecting to the lungs will be determined. The proposed experiments will be one of the first to examine how the brain regulates airway caliber.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL040910-04
Application #
3358253
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1988-07-01
Project End
1993-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Beyaert, C A; Hill, J M; Lewis, B K et al. (1998) Effect on airway caliber of stimulation of the hypothalamic locomotor region. J Appl Physiol 84:1388-94
Solomon, I C (1998) Activation of NMDA and non-NMDA receptors in the caudal ventrolateral medulla dilates the airways. J Auton Nerv Syst 74:169-74
Motekaitis, A M; Solomon, I C; Kaufman, M P (1996) Blockade of glutamate receptors in CVLM and NTS attenuates airway dilation evoked from parabrachial region. J Appl Physiol 81:400-7
Motekaitis, A M; Kaufman, M P (1996) Stimulation of the mesencephalic locomotor region constricts the airways of cats. Respir Physiol 106:263-71
Motekaitis, A M; Solomon, I C; Kaufman, M P (1995) Role of the parabrachial nuclei in the airway dilation evoked by the Hering-Breuer reflex. Brain Res 671:314-6
Motekaitis, A M; Solomon, I C; Kaufman, M P (1994) Stimulation of parabrachial nuclei dilates airways in cats. J Appl Physiol 76:1712-8
Solomon, I C; Motekaitis, A M; Wong, M K et al. (1994) NMDA receptors in caudal ventrolateral medulla mediate reflex airway dilation arising from the hindlimb. J Appl Physiol 77:1697-704
Haselton, J R; Solomon, I C; Motekaitis, A M et al. (1992) Bronchomotor vagal preganglionic cell bodies in the dog: an anatomic and functional study. J Appl Physiol 73:1122-9
Padrid, P A; Haselton, J R; Kaufman, M P (1991) Role of caudal ventrolateral medulla in reflex and central control of airway caliber. J Appl Physiol 71:2274-82
Haselton, J R; Padrid, P A; Kaufman, M P (1991) Activation of neurons in the rostral ventrolateral medulla increases bronchomotor tone in dogs. J Appl Physiol 71:210-6

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