Opioidergic modulation of ventilatory response to sustained hypoxia in obese Zucker rats.
Opioidergic modulation of ventilatory response to sustained hypoxia in obese Zucker rats.
复制标题
阿片能调节肥胖 Zucker 大鼠对持续缺氧的通气反应。
DOI：
10.1038/oby.2001.53
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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：
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作者：
Lee,SD;Magalang,UJ;Krasney,JA;Farkas,GA
目的：探讨中枢和/或外周阿片能机制改变是否参与肥胖Zucker大鼠对持续低氧的呼吸反应改变。研究方法和步骤：6周龄Zucker肥胖大鼠8只，分别为(176±8)g和(225±12)g。随机、盲法分别给予等量生理盐水(对照组)、甲碘化纳洛酮(NM；5 mg/kg，外周阿片拮抗剂)或盐酸纳洛酮(NHCl，5 mg/kg，外周和中枢阿片拮抗剂)后，用大气压法分别测定静息状态和持续低氧(30min)时的肺通气量(V̇E)、潮气量(VT)和呼吸频率(F)。结果：NM和NHClin瘦动物静息和持续低氧30min对V̇E均无影响。同样，NM未能改变肥胖大鼠的V̇E。相比之下，NHC显著增加肥胖大鼠安静时和低氧暴露2-10分钟时的V、̇、E和VT。在低氧20-30分钟后，NHCl使VT持续升高，但由于低氧20分钟时f的降低，V̇E的早期升高似乎有所减弱。讨论：因此，内源性阿片类药物通过特异性作用于中枢神经系统内的阿片受体，调节肥胖大鼠的静息V̇E和持续低氧时的呼吸机反应。
Objective:To determine whether altered central and/or peripheral opioidergic mechanisms contribute to the altered ventilatory response to sustained hypoxia in obese Zucker rats.Research Methods and Procedures:Eight lean (176 ± 8 [SEM] g) and eight obese (225 ± 12 g) Zucker rats were studied at 6 weeks of age. Pulmonary ventilation (V̇E), tidal volume (VT), and breathing frequency (f) at rest and in response to sustained (30 minutes) hypoxic (10% O2) challenges were measured on three separate occasions by the barometric method after the randomized, blinded administration of equal volumes of saline (control), naloxone methiodide (NM; 5 mg/kg, peripheral opioid antagonist), or naloxone hydrochloride (NHCl; 5 mg/kg, peripheral and central opioid antagonist).Results:Administration of NMand NHClin lean animals had no effect on V̇Eeither at rest or during 30 minutes of sustained exposure to hypoxia. Similarly, NMfailed to alter V̇Ein obese rats. In contrast, NHClsignificantly (p< 0.05) increased V̇Eand VTboth at rest and during 2 to 10 minutes of hypoxic exposure in obese rats. After 20 to 30 minutes of hypoxic exposure, VTremained elevated with NHCl, but the earlier elevation of V̇Eseemed to be attenuated due to a decrease in f at 20 minutes of exposure to hypoxia.Discussion:Thus, endogenous opioids modulate both resting V̇Eand the ventilatory response to sustained hypoxia in obese, but not in lean, Zucker rats by acting specifically on opioid receptors located within the central nervous system.