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Published ahead of print on July 15, 2004, doi:10.1164/rccm.200312-1674OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 804-810, (2004)
© 2004 American Thoracic Society
doi: 10.1164/rccm.200312-1674OC

Original Article

Systemic Administration of Serotonin 2A/2C Agonist Improves Upper Airway Stability in Zucker Rats

Toshiyuki Ogasa, Andrew D. Ray, Charles P. Michlin, Gaspar A. Farkas, Brydon J. B. Grant and Ulysses J. Magalang

Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine; Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York; and Department of Medicine, Division of Pulmonary and Critical Care Medicine, The Ohio State University, Columbus, Ohio

Correspondence and requests for reprints should be addressed to Ulysses J. Magalang, M.D., Division of Pulmonary and Critical Care Medicine, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210. 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 (BP) were measured before and after the intravenous administration of the agonist. A robust activation of the genioglossus muscle in all lean and obese rats was associated with decreased upper airway (UA) collapsibility (p < 0.05), unchanged maximum flow, and increased oronasal resistance (p < 0.05) in both groups. The changes in UA mechanics and BP after the drug were similar in lean and obese rats. The serotonin agonist had no effect on UA mechanics in a group of paralyzed (pancuronium bromide) rats, despite similar elevations in BP. There was a smaller decrease (p < 0.05) in UA 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 UA collapsibility predominantly, but not exclusively, via stimulation of the hypoglossal nerves and also increases upstream resistance, at least in part, through activation of nonhypoglossal motoneuronal pools innervating the UA muscles.

Key Words: obesity • serotonin • upper airway function




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