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mise à jour du
31 décembre 2003
J Appl Physiol
1998; 84; 1388-1394
Effect on airway caliber of stimulation of the hypothalamic locomotor region
CA Beyaert, JM Hill, BK Lewis, MP Kaufman
Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Physiology, University of California, Davis
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Abstract : Airway dilation is one of the many autonomic responses to exercise. Two neural mechanisms are believed to evoke these responses: central command and the muscle reflex. Previously, we found that activation of central command, evoked by electrical and chemical stimulation of the mesencephalic locomotor region, constricted the airways rather than dilated them. In the present study we examined in decerebrate paralyzed cats the role played by the hypothalamic locomotor region, the activation of which also evokes central command, in causing the airway dilator response to exercise. We found that activation of the hypothalamic locomotor region by electrical and chemical stimuli evoked fictive locomotion and, for the most part, airway constriction. Fictive locomotion also occurred spontaneously, and this too, for the most part, was accompanied by airway constriction. We conclude that central command plays a minor role in the airway dilator response to exercise.
Dynamic exercise evokes a large number of cardiovascularand respiratory responses, one of which is airway dilation. The neural mechanism responsible for the exercise-induced airway dilation is not known, but central command is an important candidate and is defined as the parallel activation of locomotor, ventilatory, and autonomic circuits at the onset of exercise. Central command is not dependent on feedback from the periphery.
In animals, central command can be simulated by activation of two sites: the cuneiform nucleus of the midbrain and in or near the H2 field of Forel of the posterior hypothalamus. The former site has been termed the mesencephalic locomotor region and the latter the hypothalamic locomotor region (HLR). In a recent study our laboratory showed that electrical and chemical stimulation of the mesencephalic locomotor region increased total lung resistance,an effect that was caused by the activation of cholinergic receptors on airway smooth muscle.
This finding was surprising because it provided no support for the hypothesis that central command contributed to the airway dilation evoked by dynamic exercise. In the present study we have sought support for this hypothesis by stimulating the other central command site, i.e., the HLR. In addition, we have examined the effect of fictive locomotion, occurring spontaneously, on airway caliber.
Discussion We have examined the role of the HLR in the control of airway caliber. Specifically, we tested the hypothesis that activation of this region is responsible for the airway dilation seen during dynamic exercise. Our requirements for the successful activation of the HLR, and therefore central command, were based on functional criteria. These included increases in mean arterial pressure, increases in heart rate, increases in phrenic nerve discharge, and fictive locomotion, each of which must have occurred for the data to be included in our analysis. Overall, our data were not supportive of the hypothesis that the HLR plays an important role in causing the airway dilation evoked by dynamic exercise. For example, in 70% of the 23 cats tested, electrical stimulation of the HLR constricted the airways. When dilation of the airways did occur (i.e., in ,30% of cats), its magnitude was modest. In addition, the airway constriction evoked by electrical stimulation did not appear to be an artifact caused by the activation of fibers of passage, because the same effect was caused by microinjection of picrotoxin, a GABA antagonist, which functions by blocking chloride iontophores on cell bodies and dendrites.
When stimulation of the HLR did evoke airway dilation, the response was converted by b-adrenergic blockade to airway constriction and subsequently was abolished by atropine. We can offer two explanations for the mechanism causing the airway dilator response to HLR stimulation. First, stimulation of the HLR activated b-adrenergic receptors located on airway smooth muscle. This activation could occur by the release of transmitter from sympathetic postganglionic nerves or by the release of epinephrine from the adrenal gland. Second, the pressor response to HLR stimulation evoked the baroreflex, one component of which is airway dilation. We do not know which explanation is correct, but when airway dilation was evoked by HLR stimulation, the pressor response was, on average, 18 mmHg greater than that when airway constriction was evoked by HLR stimulation. We speculate that in the seven cats showing a dilator response to HLR stimulation the large pressor effect may have been sufficient to overwhelm the airway constriction usually observed when this maneuver is initiated.
Nevertheless, electrical stimulation of the HLR for the most part evoked airway constriction, as evidenced by an increase in total lung resistance. This increase was not effected by b-adrenergic blockade but was abolished by muscarinic blockade. This finding is consistent with previous reports that the constrictor response to stimulation of the brain stem is caused by the activation of cholinergic pathways to airway smooth muscle.
If central command is not the major neural mechanism causing the exercise-induced airway dilation, then what is? Two candidates come to mind: the Hering-Breuer reflex and the muscle reflex. Both evoke bronchodilation by withdrawal of cholinergic tone to airway smooth muscle. Slowly adapting stretch receptors comprise the afferent arm of the Hering-Breuer reflex arc. The activity of these slowly adapting receptors will be increased by exerciseinduced increases in tidal volume and the rate of breathing. Similarly, group III and IV afferents comprise the afferent arm of the muscle reflex arc. The activity of these thin fiber afferents is known to be increased by dynamic exercise.
Our conclusion that activation of the HLR is not the major mechanism causing exercise-induced airway dilation applies to the tracheobronchial tree but not to the upper airways. In our experiments the cats were paralyzed, which prevented neurotransmission from the HLR to the skeletal muscles. In addition, the trachea was cannulated below the larynx, which removed the upper airways from our calculations of total lung resistance and dynamic compliance. Consequently, the role of central command in the control of the upper airways during exercise remains to be determined.
The fact that the cats used in our experiments were paralyzed and ventilated had another consequence; i.e., feedback from pulmonary stretch receptors to brainstem neurons controlling airway caliber and breathing was abnormal. In turn, afferent input from these receptors reached the brain stem out of phase with central respiratory drive. Therefore, we cannot exclude the possibility that this factor was responsible for our inability to evoke major dilation of the airways during stimulation of the HLR. We were, however, able to evoke airway dilation in our preparation when the tibial nerve was stimulated electrically (present results) or when the triceps surae muscles were contracted statically.
There is no doubt that central command plays an important role in the control of cardiovascular and ventilatory function during exercise. Indeed, central command is thought to be the dominant mechanism causing the ventilatory response to exercise).
Nevertheless, central command appears to play a minor role in the airway smooth muscle dilation known to occur during dynamic exercise. This conclusion is based on the assumption that the hypothalamic and mesencephalic locomotor regions of the decerebrate unanesthetized cat comprise the neuroanatomic substrate for central command. Other sites in the brain stem may also be involved in the generation of central command, and their effects on airway caliber will need to be investigated as these sites are identified.