Abstract：
The central CO2 chemoreflex is a vital component of respiratory control networks, providing excitatory drive during resting conditions and challenges to blood gas homeostasis. The retrotrapezoid nucleus is a crucial hub for CO2 chemosensitivity; its ablation or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Similar phenotypes characterize certain hypoventilation syndromes, suggesting underlying retrotrapezoid nucleus impairment in these disorders. Progesterone stimulates restful breathing and CO2 chemoreflexes. However, its mechanisms and sites of actions remain unknown and the experimental use of synthetic progestins in patients and animal models have been met with mixed respiratory outcomes.
We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography.
Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion-dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel-induced CO2 chemoreflex recovery.
This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.
We investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could rescue respiratory chemoreflexes following selective lesion of the retrotrapezoid nucleus with saporin toxin. Adult female Sprague Dawley rats were grouped based on lesion size determined by the number of surviving chemosensitive neurons, and ventilatory responses were measured by whole body plethysmography.
Ventilatory responses to hypercapnia (but not hypoxia) were compromised in a lesion-dependent manner. Chronic etonogestrel treatment improved CO2 chemosensitivity selectively in rats with moderate lesion, suggesting that a residual number of chemosensitive neurons are required for etonogestrel-induced CO2 chemoreflex recovery.
This study provides new evidence for the use of progestins as respiratory stimulants under conditions of central hypoventilation and provides a new testable model for assessing the mechanism of action of progestins in the respiratory network.
摘要：
目的：中枢CO2化学反射是呼吸控制网络的重要组成部分，在休息条件下提供兴奋性驱动，并挑战血气稳态。后梯形核是CO2化学敏感性的关键枢纽；它的消融或抑制作用减弱了CO2化学挠曲并减少了呼吸。类似的表型表征某些低通气综合征，提示这些疾病中潜在的后梯形核损伤。孕酮刺激呼吸和CO2化学反应。然而,其作用机制和作用部位尚不清楚,在患者和动物模型中实验性使用合成孕激素时出现混合的呼吸结局.
方法：我们研究了孕激素药物的急性或慢性给药，依托孕孕酮,皂草素毒素可以挽救后梯形核选择性损伤后的呼吸化学反射。成年雌性SpragueDawley大鼠根据存活的化学敏感神经元数量确定的病变大小进行分组，通过全身体积描记术测量通气反应。
结果：对高碳酸血症（而非缺氧）的通气反应以损伤依赖性方式受损。慢性依托孕酮治疗选择性改善中度病变大鼠的CO2化学敏感性，表明依托孕烯诱导的CO2化学反射恢复需要残留数量的化学敏感神经元。
结论：这项研究为在中枢低通气条件下使用孕激素作为呼吸兴奋剂提供了新的证据，并为评估孕激素在呼吸网络中的作用机制提供了一个新的可测试模型。
方法：我们研究了孕激素药物的急性或慢性给药，依托孕孕酮,皂草素毒素可以挽救后梯形核选择性损伤后的呼吸化学反射。成年雌性SpragueDawley大鼠根据存活的化学敏感神经元数量确定的病变大小进行分组，通过全身体积描记术测量通气反应。
结果：对高碳酸血症（而非缺氧）的通气反应以损伤依赖性方式受损。慢性依托孕酮治疗选择性改善中度病变大鼠的CO2化学敏感性，表明依托孕烯诱导的CO2化学反射恢复需要残留数量的化学敏感神经元。
结论：这项研究为在中枢低通气条件下使用孕激素作为呼吸兴奋剂提供了新的证据，并为评估孕激素在呼吸网络中的作用机制提供了一个新的可测试模型。
