Souza George Miguel P R, Bonagamba Leni G H, Amorim Mateus R, Moraes Davi J A, Machado Benedito H
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, SP, Brazil.
Exp Physiol. 2016 Nov 1;101(11):1345-1358. doi: 10.1113/EP085850. Epub 2016 Oct 17.
What is the central question of the study? There are sex differences in the respiratory network and in the regulation of arterial blood pressure. Female rats develop hypertension after chronic intermittent hypoxia (CIH). In this context, we evaluated the respiratory-related mechanism underlying the development of hypertension in CIH-exposed female rats. What is the main finding and its importance? Female rats exposed to CIH develop changes in the respiratory pattern related to inspiration and sympathetic overactivity phase locked to the inspiratory phase of the respiratory cycle, which is different from CIH-exposed male rats. These data suggest a specific respiratory mechanism for sympathetic overactivity in hypertensive CIH-exposed female rats. Chronic intermittent hypoxia (CIH) induces sympathetic overactivity and hypertension in male rats. Enhanced respiratory modulation of sympathetic activity in juvenile male rats exposed to CIH occurs in the expiratory phase of the respiratory cycle, characterizing changes in respiratory-sympathetic coupling. Different from other experimental models of hypertension, CIH induces an increase in arterial pressure in adult female rats similar to that observed in male rats. However, the mechanisms underlying the hypertensive phenotype in CIH-exposed female rats remain to be elucidated. Moreover, several lines of evidence have documented sex differences in respiratory network activity in response to hypoxia. Considering that CIH-exposed male rats present an increase in the respiratory modulation of sympathetic activity and there are sex differences in the respiratory network, we hypothesized that CIH-exposed female rats develop an increase in the respiratory modulation of sympathetic activity different from CIH-exposed male rats. In this study, we investigated sympathetic and respiratory activities in juvenile female rats exposed to CIH using an in situ working heart-brainstem preparation. The CIH-exposed female rats developed changes in the respiratory pattern and changes in the respiratory-sympathetic coupling marked by sympathetic overactivity phase locked to inspiration, which was different from male rats exposed to CIH. This study revealed a specific respiratory-related mechanism for sympathetic overactivity linked to inspiration that explains, at least in part, the hypertensive phenotype in female rats exposed to CIH.
该研究的核心问题是什么？呼吸网络以及动脉血压调节存在性别差异。慢性间歇性低氧（CIH）后雌性大鼠会发生高血压。在此背景下，我们评估了CIH暴露雌性大鼠高血压发生背后与呼吸相关的机制。主要发现及其重要性是什么？暴露于CIH的雌性大鼠出现与吸气相关的呼吸模式变化以及与呼吸周期吸气相锁相的交感神经过度活跃，这与CIH暴露的雄性大鼠不同。这些数据表明，在CIH暴露的高血压雌性大鼠中，交感神经过度活跃存在特定的呼吸机制。慢性间歇性低氧（CIH）会诱导雄性大鼠交感神经过度活跃和高血压。暴露于CIH的幼年雄性大鼠交感神经活动的呼吸调节增强发生在呼吸周期的呼气阶段，这是呼吸-交感耦合变化的特征。与其他高血压实验模型不同，CIH会使成年雌性大鼠的动脉血压升高，与雄性大鼠中观察到的情况相似。然而，CIH暴露雌性大鼠高血压表型背后的机制仍有待阐明。此外，有几条证据记录了呼吸网络活动对低氧反应的性别差异。鉴于CIH暴露的雄性大鼠交感神经活动的呼吸调节增加，且呼吸网络存在性别差异，我们推测CIH暴露的雌性大鼠交感神经活动的呼吸调节增加，且与CIH暴露的雄性大鼠不同。在本研究中，我们使用原位工作心脏-脑干标本研究了CIH暴露幼年雌性大鼠的交感神经和呼吸活动。CIH暴露的雌性大鼠出现了呼吸模式变化以及以与吸气锁相的交感神经过度活跃为特征的呼吸-交感耦合变化，这与CIH暴露的雄性大鼠不同。这项研究揭示了一种与吸气相关的交感神经过度活跃的特定呼吸机制，这至少部分解释了CIH暴露雌性大鼠的高血压表型。
