Role of nitric oxide in thermoregulation and hypoxic ventilatory response in obese Zucker rats.
Role of nitric oxide in thermoregulation and hypoxic ventilatory response in obese Zucker rats.
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DOI：
10.1164/ajrccm.164.3.2010142
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发表时间：
2001-08
影响因子：
24.7
通讯作者：
H. Nakano;Shin-Da Lee;ANDREW D. Ray-ANDREW D.-Ray-2239729907;J. Krasney;G. Farkas
中科院分区：
文献类型：
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作者：
H. Nakano;Shin-Da Lee;ANDREW D. Ray-ANDREW D.-Ray-2239729907;J. Krasney;G. Farkas
为了研究一氧化氮 (NO) 对肥胖患者体温调节和呼吸控制的作用，清醒肥胖和年龄匹配的瘦 Zucker (Z) 大鼠接受了持续的缺氧挑战。腹腔内给予 100 mg/kg N(G)-硝基-L-精氨酸甲酯 (L-NAME)（一种非特异性 NOS 抑制剂）、25 mg/kg 7-硝基吲唑 (7-NI)（一种选择性神经元 NOS）后，在室内空气和 30 分钟缺氧 (10% O(2)) 期间测量体温 (Tb)、耗氧量 (V O(2)) 和通气量 (V E)抑制剂，或等体积的载体（二甲基亚砜：DMSO）作为对照。肥胖大鼠在室内空气中的结核分枝杆菌显着低于瘦大鼠。与肥胖大鼠相比，缺氧导致瘦大鼠的 Tb 和 V O(2) 下降更明显。与室内空气中的对照相比，L-NAME 后瘦 Z 大鼠的 Tb 显着下降约 0.2 摄氏度，更明显的是，7-NI 后约 1.1 摄氏度，而肥胖 Z 大鼠的 Tb 不受影响。 L-NAME 和 7-NI 可以减轻瘦大鼠中缺氧引起的体温过低或代谢低下，但不能减轻肥胖大鼠中的情况。瘦大鼠在缺氧时表现出 V E 突然增加，随后 V E 逐渐下降。相反，肥胖大鼠的 V E 最初增加，在持续缺氧期间趋于稳定。与对照瘦大鼠相比，L-NAME 和 7-NI 在室内空气和缺氧期间均会导致 V E 显着降低，而肥胖大鼠中的 V E 实际上不受这两种药物的影响。目前的结果表明，肥胖 Z 大鼠对缺氧的体温调节和通气反应减弱可能归因于中枢神经系统中 NOS 活性的降低。
To examine the role of nitric oxide (NO) on thermoregulation and control of breathing in obesity, awake obese and age-matched lean Zucker (Z) rats underwent a sustained hypoxic challenge. Body temperature (Tb), oxygen consumption (V O(2)) and ventilation (V E) were measured during room air and during 30-min of hypoxia (10% O(2)) after intraperitoneal administration of either 100 mg/kg of N(G)-nitro-L-arginine methyl ester (L-NAME), a nonspecific NOS inhibitor, 25 mg/kg of 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, or equal volume of vehicle (dimethyl sulfoxide: DMSO) as control. Tb in obese rats during room air was significantly lower than that of lean rats. Hypoxia induced a more pronounced drop in Tb and V O(2) in lean rats than in obese rats. Tb in lean Z rats dropped significantly by approximately 0.2 degrees C after L-NAME and, more markedly, by approximately 1.1 degrees C after 7-NI compared with control during room air, whereas Tb in obese Z rats was unaffected. L-NAME and 7-NI attenuated hypoxia-induced hypothermia or hypometabolism in lean rats, but not in obese rats. Lean rats exhibited an abrupt increase in V E in response to hypoxia followed by a gradual decline in V E. In contrast, obese rats displayed an initial increase in V E that plateaued during sustained hypoxia. Both L-NAME and 7-NI induced marked decreases in V E during room air and hypoxia compared with control lean rats, whereas V E was virtually unaffected by either agent in obese rats. The present results suggest that the blunted thermoregulatory and ventilatory responses to hypoxia in obese Z rats may be attributed to reduced activity of NOS in the central nervous system.