NMDA receptor-mediated modulation of ventilation in obese Zucker rats.
NMDA receptor-mediated modulation of ventilation in obese Zucker rats.
复制标题
NMDA 受体介导的肥胖 Zucker 大鼠通气调节。
DOI：
10.1038/sj.ijo.0801663
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Farkas,GA
中科院分区：
文献类型：
--
作者：
Lee,SD;Nakano,H;Farkas,GA
背景技术背景：在某些肥胖人群中，对缺氧的通气反应降低，并且被认为是肥胖低通气综合征（OHS）发病机制的一部分。低氧暴露引起的通气与兴奋性神经递质的释放密切相关，特别是谷氨酸，谷氨酸特异性作用于N-甲基-D-天冬氨酸（NMDA）受体。实验目的：本研究的目的是研究NMDA受体介导的机制是否是肥胖Zucker（Z）大鼠对持续低氧的通气反应改变的原因。7瘦和7个15周龄的肥胖雄性Z大鼠studied.MEASUREMENTS：通气（V今E）在休息和持续缺氧（10%O2）暴露30分钟期间，通过气压法进行了测量。随机盲法给药等体积的生理盐水（溶媒）或非竞争性谷氨酸NMDA受体拮抗剂二甲双胍（DM，10 mg/kg）后，测定V ~ E。结果：DM对瘦大鼠和肥胖大鼠的静息V ~ E无影响。结果表明，DM可显著降低消瘦大鼠的VT、VT和VT/TI，在低氧诱导的早期（5 min）和晚期（30 min）均显著降低（P< 0.05）。与此相反，在肥胖大鼠中，DM给药在低氧诱导反应的早期阶段不改变VT、VT或VT/TI。在缺氧反应的晚期。DM处理的肥胖大鼠表现出类似的抑郁症在V TOE和V T中观察到在瘦大鼠，但没有显着的变化在VT/T I在30 min缺氧exposure.CONCLUSION：我们的研究结果表明，改变的NMDA受体的兴奋机制是部分负责的迟钝的早期阶段，缺氧注意到肥胖大鼠，也有助于他们减少神经呼吸驱动。
BACKGROUND: Ventilation in response to hypoxia is reduced in some obese humans and is believed to represent part of the pathogenesis of obesity hypoventilation syndrome (OHS). Ventilation in response to hypoxic exposure is closely related to the release of excitatory neurotransmitters, in particular glutamate, acting specifically on N-methyl-D-aspartate (NMDA) receptors.OBJECTIVES: The aim of the present study was to investigate whether NMDA receptor-mediated mechanisms are responsible for the altered ventilatory response to sustained hypoxia observed in obese Zucker (Z) rats.SUBJECTS: Seven lean and seven 15-week-old obese male Z rats were studied.MEASUREMENTS: Ventilation (V̇ E) at rest and during 30 min sustained hypoxic (10% O 2) exposure was measured by the barometric method. V̇ E was assessed following the blinded-random administration of equal volumes of either saline (vehicle) or dextromethorphan (DM, 10 mg/kg), a non-competitive glutamate NMDA receptor antagonist.RESULTS: DM had no effects on resting V̇ E in both lean and obese rats during room air breathing. Lean rats treated with DM exhibited a significant (P< 0.05) depression in V̇ E, V T, and V T/T I during either the early (5 min) or the late phase (30 min) of ventilatory response to sustained hypoxia. In contrast, DM administration in obese rats did not change V̇ E, V T, or V T/T I during the early phase of ventilatory response to hypoxia. During the late phase of ventilatory response to hypoxia. obese rats treated with DM exhibited a similar depression in V̇ E and V T as observed in lean rats, but had no significant change in V T/T I during the 30 min hypoxic exposure.CONCLUSION: Our findings indicate that altered glutamatergic mechanisms acting on NMDA receptors are partially responsible for a blunted early phase of ventilatory response to hypoxia noted in obese rats and also contribute to their reduced neural respiratory drive.