Serotonergic modulation of ventilation and upper airway stability in obeseZucker rats

To elucidate the role of serotonin in the maintenance of normal breathing a nd upper airway (UA) patency in obesity, we studied the effects of systemic administration of ritanserin, a serotonin (5-HT) 2A and 2C receptor antago nist, on ventilation ((V)over dotE) during room air breathing and during hy poxic (10% O-2) and hypercapnic (4% CO2) ventilatory challenges in awake yo ung (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)over dotE (439 +/- 35 [SD] t o 386 +/- 41 ml/kg/min, p < 0.01), a decrease in respiratory rate, a prolon gation of inspiratory time, and an increase in (V)Over doto(2) (16.4 <plus/ minus> 1.7 to 18.2 +/- 1.9 ml/kg(0.75)/min, p < 0.05) during room air breat hing. 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 signific antly 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 <plus/minus> 1.0 to -2.4 +/- 0.6 cm H2O, p < 0.05). We suggest that the 5-HT2A/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 ser otonergic control of UA dilator muscles as a mechanism to prevent pharyngea l collapse.