Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia
Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia
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DOI：
10.1098/rspb.2014.1722
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发表时间：
2015-02-07
影响因子：
4.7
通讯作者：
Milsom, William K.
中科院分区：
文献类型：
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作者：
Pamenter, Matthew E.;Dzal, Yvonne A.;Milsom, William K.
裸鼹鼠是最耐缺氧的哺乳动物;然而，这种耐受性的机制知之甚少。采用全动物体积描记法和开放流呼吸法，观察了清醒、自由活动的裸鼹鼠暴露于7%O2 1h后的低氧代谢反应（HMR）、低氧呼吸反应（HVR）和低氧热反应。在缺氧状态下，代谢率和通气量均可逆性降低70%（分别从39.6 +/-2.9降至12.1 +/-0.3 ml O-2 min（-1）kg（-1），从1412 +/-244降至417 +/-62 ml min（-1）kg（-1）; p <0.05），而体温不变，动物保持清醒和活动。皮下注射一般腺苷受体拮抗剂氨茶碱（AMP; 100 mg kg（-1），在盐水中），但不是对照盐水注射，防止HVR，但对HMR没有影响。结果，AMP处理的裸鼹鼠在缺氧时表现出极端的过度换气。这些动物对缺氧的耐受性也较低，在某些情况下，AMP注射后缺氧是致命的。我们的结论是，在裸鼹鼠（i）缺氧耐受性是部分依赖于深刻的缺氧代谢和代谢反应，这是相等的幅度，但发生独立的缺氧热变化，和（ii）腺苷受体介导的HVR，但不是HMR。
Naked mole rats are the most hypoxia-tolerant mammals identified; however, the mechanisms underlying this tolerance are poorly understood. Using whole-animal plethysmography and open-flow respirometry, we examined the hypoxic metabolic response (HMR), hypoxic ventilatory response (HVR) and hypoxic thermal response in awake, freely behaving naked mole rats exposed to 7% O-2 for 1 h. Metabolic rate and ventilation each reversibly decreased 70% in hypoxia (from 39.6 +/- 2.9 to 12.1 +/- 0.3 ml O-2 min(-1) kg(-1), and 1412 +/- 244 to 417 +/- 62 ml min(-1) kg(-1), respectively; p < 0.05), whereas body temperature was unchanged and animals remained awake and active. Subcutaneous injection of the general adenosine receptor antagonist aminophylline (AMP; 100 mg kg(-1), in saline), but not control saline injections, prevented the HVR but had no effect on the HMR. As a result, AMP-treated naked mole rats exhibited extreme hyperventilation in hypoxia. These animals were also less tolerant to hypoxia, and in some cases hypoxia was lethal following AMP injection. We conclude that in naked mole rats (i) hypoxia tolerance is partially dependent on profound hypoxic metabolic and ventilatory responses, which are equal in magnitude but occur independently of thermal changes in hypoxia, and (ii) adenosine receptors mediate the HVR but not the HMR.