Fournier Sebastien, Allard Mathieu, Gulemetova Roumiana, Joseph Vincent, Kinkead Richard
Department of Pediatrics, Centre de Recherche Hospitalier Universitaire de Québec, Université Laval, Québec, QC, Canada.
J Physiol. 2007 Nov 1;584(Pt 3):951-62. doi: 10.1113/jphysiol.2007.141655. Epub 2007 Sep 13.
Perinatal stress disrupts normal development of the hypothalamo-pituitary-adrenal (HPA) axis. Adult male (but not female) rats previously subjected to a stress such as neonatal maternal separation (NMS) are characterized by chronic elevation of plasma corticosterone (Cort) levels and an abnormally elevated hypoxic ventilatory response through mechanisms that remain unknown. The present study tested the hypothesis that a chronic increase of plasma Cort levels alone augments the ventilatory response to hypoxia in adult rats. Three groups of Sprague-Dawley male and female rats were used (control, placebo and Cort implants). Rats subjected to chronic Cort elevation received a subcutaneous Cort implant (300 mg) 14 days prior to ventilatory measurements, whereas sham-operated rats received placebo implants. Controls received no treatment. Plasma Cort levels and body weight profiles were measured to assess protocol efficiency. Whole body plethysmography was used to measure ventilatory activity and metabolic indices during normoxia and following a 20 min period of moderate hypoxia (12% O(2)). Male rats implanted with Cort showed a ventilatory response to hypoxia higher than placebo-treated rats; this effect was mainly due to a larger tidal volume response. In females, Cort treatment increased the breathing frequency response but the effect on minute ventilation was not significant. Taken together, these data show that chronic elevation of Cort alone increases the ventilatory response to hypoxia, but in a sex-specific manner. These data raise important questions regarding the mechanisms underlying the sexual dimorphism of this effect and the potential link between HPA axis dysfunction and respiratory disorders related to abnormal ventilatory chemoreflex.
围产期应激会破坏下丘脑-垂体-肾上腺（HPA）轴的正常发育。成年雄性（而非雌性）大鼠若先前经历过诸如新生鼠母婴分离（NMS）这样的应激，其特征为血浆皮质酮（Cort）水平持续升高，以及通过尚不明的机制导致异常升高的低氧通气反应。本研究检验了如下假设：仅血浆Cort水平的持续升高就会增强成年大鼠对低氧的通气反应。使用了三组Sprague-Dawley雄性和雌性大鼠（对照组、安慰剂组和皮质酮植入组）。经历皮质酮持续升高的大鼠在进行通气测量前14天接受皮下皮质酮植入（300毫克），而假手术大鼠接受安慰剂植入。对照组不接受任何处理。测量血浆Cort水平和体重变化情况以评估实验方案的有效性。使用全身体积描记法测量常氧状态下以及20分钟中度低氧（12% O₂）期间的通气活动和代谢指标。植入皮质酮的雄性大鼠对低氧的通气反应高于接受安慰剂处理的大鼠；这种效应主要归因于更大的潮气量反应。在雌性大鼠中，皮质酮处理增加了呼吸频率反应，但对分钟通气量的影响不显著。综上所述，这些数据表明，仅皮质酮的持续升高就会增加对低氧的通气反应，但存在性别特异性。这些数据就这种效应的性别差异背后的机制以及HPA轴功能障碍与异常通气化学反射相关的呼吸障碍之间的潜在联系提出了重要问题。
