Nakano H, Magalang U J, Lee S D, Krasney J A, Farkas G A
Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, New York, USA.
Am J Respir Crit Care Med. 2001 Apr;163(5):1191-7. doi: 10.1164/ajrccm.163.5.2004230.
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.
为了阐明血清素在肥胖状态下维持正常呼吸及上呼吸道（UA）通畅中的作用，我们研究了系统给予利坦色林（一种血清素（5-羟色胺，5-HT）2A和2C受体拮抗剂）对清醒的年轻（6 - 8周）及年长（7 - 8个月）肥胖和瘦素 Zucker（Z）大鼠在室内空气呼吸时以及在低氧（10% O2）和高碳酸血症（4% CO2）通气挑战期间通气（VE）的影响。年长的肥胖Z大鼠与年长的瘦素大鼠相比，采用了更快的浅呼吸模式。给年长的肥胖大鼠腹腔注射利坦色林（1 mg/kg）导致在室内空气呼吸时VE降低（从439 ± 35 [标准差]降至386 ± 41 ml/kg/min，p < 0.01），呼吸频率降低，吸气时间延长，以及VO2增加（从16.4 ± 1.7增至18.2 ± 1.9 ml/kg(0.75)/min，p < 0.05）。相比之下，它对年轻的瘦素和肥胖Z大鼠或年长的瘦素Z大鼠的通气影响很小。利坦色林对年轻或年长的瘦素和肥胖Z大鼠对低氧或高碳酸血症的通气反应也没有影响。我们检查了年长Z大鼠离体UA的可塌陷性。年长肥胖大鼠的咽部临界压力（Pcrit）显著高于瘦素大鼠（p < 0.05），表明肥胖大鼠的UA比瘦素大鼠更易塌陷。给年长肥胖大鼠和瘦素大鼠注射利坦色林显著增加了Pcrit（年长肥胖大鼠从 - 1.6 ± 0.3升至 - 0.8 ± 0.2 cm H2O，p < 0.01；瘦素大鼠从 - 3.1 ± 1.0升至 - 2.4 ± 0.6 cm H2O，p < 0.05）。我们认为5-HT(2A/2C)受体亚型在肥胖状态下维持UA稳定性和正常呼吸中起重要作用，并且我们推测年长的肥胖Z大鼠可能增强了对UA扩张肌的血清素能控制，作为防止咽部塌陷的一种机制。
