title: Serotonergic modulation of ventilation and upper airway stability in obese Zucker rats.
abstract: To elucidate the role of serotonin in the maintenance of normal breathing and upper airway (UA) patency in obesity, we studied the effects of systemic administration of ritanserin, a serotonin (5-HT) 2A and 2C receptor antagonist, on ventilation (V E) during room air breathing and during hypoxic (10% O2) and hypercapnic (4% CO2) ventilatory challenges in awake young (6-8 wk) and older (7-8 mo) obese and lean Zucker (Z) rats. Older obese Z rats adopted a more rapid shallow breathing pattern compared with older lean rats. The administration of ritanserin (1 mg/kg intraperitoneally) to older obese rats resulted in a reduction in V E (439 +/- 35 [SD] to 386 +/- 41 ml/kg/min, p < 0.01), a decrease in respiratory rate, a prolongation of inspiratory time, and an increase in V O2 (16.4 +/- 1.7 to 18.2 +/- 1.9 ml/kg(0.75)/min, p < 0.05) during room air breathing. By comparison, it had little effect on ventilation in young lean and obese Z or older lean Z rats. Ritanserin also had no effect on ventilatory responses to either hypoxia or hypercapnia in young or older lean and obese Z rats. The collapsibility of the isolated UA was examined in older Z rats. The pharyngeal critical pressure (Pcrit) of older obese rats was significantly greater than that of lean rats (p < 0.05), indicating that obese rats have more collapsible UA than lean rats. The administration of ritanserin significantly increased Pcrit in older obese rats (-1.6 +/- 0.3 to -0.8 +/- 0.2 cm H2O, p < 0.01) and in lean rats (-3.1 +/- 1.0 to -2.4 +/- 0.6 cm H2O, p < 0.05). We suggest that the 5-HT(2A/2C) receptor subtype plays an important role in the maintenance of UA stability and normal breathing in obesity, and we speculate that older obese Z rats may have augmented serotonergic control of UA dilator muscles as a mechanism to prevent pharyngeal collapse.
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York, USA.
authors.forename: H
authors.initials: H
authors.lastname: Nakano
authors.forename: U J
authors.initials: UJ
authors.lastname: Magalang
authors.forename: S D
authors.initials: SD
authors.lastname: Lee
authors.forename: J A
authors.initials: JA
authors.lastname: Krasney
authors.forename: G A
authors.initials: GA
authors.lastname: Farkas
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D006935:Hypercapnia / Q000503:physiopathology; D018496:Hyperoxia / Q000503:physiopathology; D016014:Linear Models; D009765:Obesity / Q000503:physiopathology*; D010991:Plethysmography; D012123:Pulmonary Ventilation / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D015656:Respiratory Mechanics / Q000187:drug effects*; D016713:Ritanserin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D016037:Single-Blind Method
chemical_list: D012702:Serotonin Antagonists; D016713:Ritanserin