Sood Sandeep, Liu Xia, Liu Hattie, Horner Richard L
Department of Medicine, Rm. 6368, Medical Sciences Bldg., 1 Kings College Circle, University of Toronto, ON, Canada, M5S 1A8.
J Appl Physiol (1985). 2007 Jun;102(6):2240-50. doi: 10.1152/japplphysiol.01229.2006. Epub 2007 Mar 1.
Obese Zucker rats have a narrower and more collapsible upper airway compared with lean controls, similar to obstructive sleep apnea (OSA) patients. Genioglossus (GG) muscle activity is augmented in awake OSA patients to compensate for airway narrowing, but the neural control of GG activity in obese Zucker rats has not been investigated to determine whether such neuromuscular compensation also occurs. This study tests the hypotheses that GG activity is augmented in obese Zucker rats compared with lean controls and that endogenous 5-hydroxytryptamine (5-HT) contributes to GG activation. Seven obese and seven lean Zucker rats were implanted with electroencephalogram and neck muscle electrodes to record sleep-wake states, and they were implanted with GG and diaphragm wires for respiratory muscle recordings. Microdialysis probes were implanted into the hypoglossal motor nucleus for perfusion of artificial cerebrospinal fluid and the 5-HT receptor antagonist mianserin (100 microM). Compared with lean controls, respiratory rates were increased in obese rats across sleep-wake states (P=0.048) because of reduced expiratory durations (P=0.007); diaphragm activation was similar between lean and obese animals (P=0.632). Respiratory-related, tonic, and peak GG activities were also similar between obese and lean rats (P>0.139). There was no reduction in GG activity with mianserin at the hypoglossal motor nucleus, consistent with recent observations of a minimal contribution of endogenous 5-HT to GG activity. These results suggest that despite the upper airway narrowing in obese Zucker rats, these animals have a sufficiently stable airway such that pharyngeal muscle activity is normal across sleep-wake states.
与瘦素对照组相比，肥胖的 Zucker 大鼠上呼吸道更狭窄且更易塌陷，这与阻塞性睡眠呼吸暂停（OSA）患者相似。清醒的 OSA 患者颏舌肌（GG）活动增强以补偿气道狭窄，但尚未对肥胖 Zucker 大鼠 GG 活动的神经控制进行研究，以确定是否也会发生这种神经肌肉补偿。本研究检验了以下假设：与瘦素对照组相比，肥胖 Zucker 大鼠的 GG 活动增强，且内源性 5-羟色胺（5-HT）有助于 GG 激活。给 7 只肥胖和 7 只瘦素 Zucker 大鼠植入脑电图和颈部肌肉电极以记录睡眠-觉醒状态，并植入 GG 和膈肌导线以记录呼吸肌活动。将微透析探针植入舌下运动核，用于灌注人工脑脊液和 5-HT 受体拮抗剂米安色林（100 microM）。与瘦素对照组相比，肥胖大鼠在整个睡眠-觉醒状态下呼吸频率增加（P = 0.048），原因是呼气持续时间缩短（P = 0.007）；瘦素和肥胖动物之间的膈肌激活相似（P = 0.632）。肥胖和瘦素大鼠之间与呼吸相关的、紧张性的和峰值 GG 活动也相似（P>0.139）。在舌下运动核，米安色林并未降低 GG 活动，这与最近关于内源性 5-HT 对 GG 活动贡献极小的观察结果一致。这些结果表明，尽管肥胖 Zucker 大鼠上呼吸道狭窄，但这些动物的气道足够稳定，以至于在整个睡眠-觉醒状态下咽部肌肉活动正常。
