Submitted on September 23, 2008
Revised on April 7, 2009
Accepted on April 19, 2009
Dorsomedial medullary 5-HT2 receptors mediate immediate onset of initial hyperventilation, airway dilation and ventilatory decline during hypoxia in mice
Mitsuko Kanamaru1* and Ikuo Homma1
1 Showa University School of Medicine
* To whom correspondence should be addressed. E-mail: mitsuko{at}med.showa-u.ac.jp.
The dorsomedial medulla oblongata (DMM) includes the solitary tract nucleus and the hypoglossal nucleus, to which 5-HT neurons project. Effects of 5-HT in the DMM on ventilatory augmentation and airway dilation are mediated via 5-HT2 receptors, which interact with the CO2 drive. The interaction may elicit cycles between hyperventilation with airway dilation and hypoventilation with airway narrowing. In the present study, effects of 5-HT2 receptors in the DMM on hypoxic ventilatory and airway responses were investigated, while 5-HT release in the DMM was monitored. Adult male mice were anesthetized and then a microdialysis probe was inserted into the DMM. The mice were placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to hypoxic gas (7% O2 in N2) for 5 min with or without a 5-HT2 receptor antagonist (LY-53857) perfused in the DMM. 5-HT release in the DMM was increased by hypoxia regardless of the presence of LY-53857. Immediate onset and the peak of initial hypoxic hyperventilatory responses were delayed. Subsequent ventilatory decline and airway dilation during initial hypoxic hyperventilation were suppressed with LY-53857. These results suggest that 5-HT release increased by hypoxia acts on 5-HT2 receptors in the DMM, which contributes to the immediate onset of initial hypoxic hyperventilation, airway dilation, and subsequent ventilatory decline. Hypoxic ventilatory and airway responses mediated via 5-HT2 receptors in the DMM may play roles in immediate rescue and defensive adaptation for hypoxia, and may be included in periodic breathing and the pathogenesis of OSA.
