Compensatory airway dilation and additive ventilatory augmentation mediated by dorsomedial medullary 5-hydroxytryptamine 2 receptor activity and hypercapnia.
5-HT2 receptor activity in the hypoglossal nucleus and hypercapnia is associated with airway dilation. 5-HT neurons in the medullary raphe and hypercapnia are responsible for tidal volume change. In this study, the effects of 5-HT2 receptors in the dorsomedial medulla oblongata (DMM), which receives projections from the medullary raphe, and hypercapnia on airway resistance and respiratory variables were studied in mice while monitoring 5-HT release in the DMM. A microdialysis probe was inserted into the DMM of anesthetized adult mice. Each mouse was placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to stepwise increases in CO(2) inhalation (5%, 7%, and 9% CO(2) in O(2)) at 8-min intervals with a selective serotonin reuptake inhibitor, fluoxetine, or fluoxetine plus a 5-HT2 receptor antagonist, LY-53857 in the DMM. In response to fluoxetine plus LY-53857 coperfusion, specific airway resistance was increased, and tidal volume and minute ventilation were decreased. CO(2) inhalation with fluoxetine plus LY-53857 coperfusion in the DMM largely decreased airway resistance and additively increased minute ventilation. Thus, 5-HT2 receptor activity in the DMM increases basal levels of airway dilation and ventilatory volume, dependent on central inspiratory activity and the volume threshold of the inspiratory off-switch mechanism. Hypercapnia with low 5-HT2 receptor activity in the DMM largely recovers airway dilation and additively increases ventilatory volume. Interaction between 5-HT2 receptor activity in the DMM and CO(2) drive may elicit a cycle of hyperventilation with airway dilation and hypoventilation with airway narrowing.
Kanamaru
Mitsuko
M
Department of Physiology, Showa University School of Medicine, 1-5-8 Hatanodai, Shina gawa-ku, Tokyo 142-8555, Japan.
Homma
Ikuo
I
D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D006935:Hypercapnia / Q000503:physiopathology*; D007002:Hypoglossal Nerve / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D044348:Receptors, Serotonin, 5-HT2 / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D017552:Solitary Nucleus / Q000502:physiology*
D002245:Carbon Dioxide; D004873:Ergolines; D005473:Fluoxetine; D044348:Receptors, Serotonin, 5-HT2; D012701:Serotonin; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C032663:LY 53857