Episodic hypoxia enhances late hypoxic ventilation in developing rat: putative role of neuronal NO synthase.
Episodic hypoxia enhances late hypoxic ventilation in developing rat: putative role of neuronal NO synthase.
复制标题
阵发性缺氧增强发育中大鼠的后期缺氧通气：神经元 NO 合酶的推定作用。
DOI：
10.1152/ajpregu.1999.276.1.r17
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Gozal,E
中科院分区：
文献类型：
--
作者：
Gozal,D;Gozal,E
一氧化氮（NO）是缺氧性反应（HVR）中的兴奋性神经递质。此外，神经元型一氧化氮合酶（nNOS）的活性在发育中的大鼠与晚期缺氧性抑郁症的程度。为了验证这一假设，反复短暂暴露于缺氧可能会改变年轻大鼠的晚期HVR特征，我们进行了30分钟的缺氧挑战，在2至3日龄的大鼠幼崽，之前（前）和6小时后（后），他们完成了一系列的8个周期，包括5分钟的缺氧和10分钟的常氧（Hyp-Norm）或常氧整个（Norm-Norm）。在另一组中，在腹膜内给予载体或25 mg/kg 7-硝基吲唑（7-NI）后进行类似的激发。使用全身体积描记法测量通气量（V stece）。尽管在间歇性缺氧时，峰V stece-response没有发生变化（Pre vs. Post，P=无显著性），但Post时晚期V stece-response明显减弱（ΔV stece-response从早期到晚期：Pre为7.2 ± 1.5 ml/min，Post为4.5 ± 1.1 ml/min;P< 0.002）。此外，7-NI治疗后的动物与Hyp-Norm暴露动物的晚期肿瘤缩小至Pre水平相关。尾侧脑干蛋白质免疫印迹显示Hyp-Norm组nNOS表达较Norm-Norm组明显增强（P< 0.01）。目前的研究结果表明，反复短时间缺氧暴露提高维持V stece的能力，这似乎是通过增加脑干呼吸区的nNOS表达和活性介导的。我们推测nNOS的变化可能在呼吸控制可塑性中起作用。
Nitric oxide (NO) is an excitatory neurotransmitter in the hypoxic ventilatory response (HVR). Furthermore, neuronal NO synthase (nNOS) activity in the developing rat correlates with the magnitude of late hypoxic ventilatory depression. To test the hypothesis that repeated short exposures to hypoxia may modify late HVR characteristics in young rats, we conducted 30-min hypoxic challenges in 2- to 3-day-old rat pups, before (Pre) and 6 h after (Post) they completed a series of eight cycles consisting of 5 min of hypoxia and 10 min of normoxia (Hyp-Norm) or normoxia throughout (Norm-Norm). In an additional group, similar challenges were performed after administration of either intraperitoneal vehicle or 25 mg/kg 7-nitroindazole (7-NI). Ventilation (V˙e) was measured using whole body plethysmography. Although no changes in peakV˙eresponses occurred with episodic hypoxia (Pre vs. Post,P= not significant), lateV˙ereductions were markedly attenuated in Post (ΔV˙efrom early to late: 7.2 ± 1.5 ml/min in Pre vs. 4.5 ± 1.1 ml/min in Post;P< 0.002). Furthermore, 7-NI treatment of Post animals was associated with lateV˙ereductions to Pre levels in Hyp-Norm-exposed animals. Western blots of protein equivalents from the caudal brain stem revealed increased nNOS expression in Hyp-Norm compared with Norm-Norm (P< 0.01). Current findings suggest that repeated short hypoxic exposures improve the ability to sustain V˙e, which appears to be mediated by increased nNOS expression and activity in brain stem respiratory regions. We postulate that changes in nNOS may play a role in respiratory control plasticity.