Published ahead of print on July 15, 2004, doi:10.1164/rccm.200312-1674OC Am. J. Respir. Crit. Care Med., Volume 170, Number 7, October 2004, 804-810 A more recent version of this article appeared on October 1, 2004
Submitted on December 11, 2003 Systemic Administration of Serotonin 2A/2C Agonist Improves Upper Airway Stability in Zucker RatsToshiyuki Ogasa1,1 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Buffalo, NY, USA; Department of Medicine, Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus, OH, USA, 2 Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY, USA, 3 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Buffalo, NY, USA; Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY, USA, 4 Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, University at Buffalo, Buffalo, NY, USA * To whom correspondence should be addressed. E-mail: magalang-1{at}medctr.osu.edu.
The effects of [±]-2,5-Dimethoxy-4-iodoaminophentamine, a serotonin2A/2C receptor agonist, on pharyngeal airflow mechanics were examined in isoflurane-anesthetized lean and obese Zucker rats. The pharyngeal pressure associated with flow limitation, maximum inspiratory flow, oronasal resistance, genioglossus muscle activity, and arterial blood pressure were measured before and after intravenous administration of the agonist. A robust activation of the genioglossus muscle in all lean and obese rats was associated with decreased upper airway collapsibility (p<0.05), unchanged maximum flow, and increased oronasal resistance (p<0.05) in both groups. The changes in upper airway mechanics and blood pressure after the drug were similar in lean and obese rats. The serotonin agonist had no effect on upper airway mechanics in a group of paralyzed (pancuronium bromide) rats, despite similar elevations in blood pressure. There was a smaller decrease (P<0.05) in upper airway collapsibility that was also associated with increased upstream resistance when the drug was administered after bilateral hypoglossal nerve transection. We conclude that systemic administration of a serotonin2A/2C receptor agonist improves upper airway collapsibility predominantly, but not exclusively, via stimulation of the hypoglossal nerves and also increases upstream resistance, at least in part, through activation of non-hypoglossal motoneuronal pools innervating the upper airway muscles. Key words: serotonin, obesity, upper airway function
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