Souza George Miguel P R, 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.
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900, SP, Brazil.
Respir Physiol Neurobiol. 2018 Oct;256:109-118. doi: 10.1016/j.resp.2017.09.003. Epub 2017 Sep 8.
Obstructive sleep apnea (OSA) is a complex disease in which humans face episodes of intermittent hypoxia and it affects men and women. Patients with OSA present hypertension and sympathetic overactivity among several other dysfunctions. Therefore, one important question remains: are the autonomic dysfunctions associated with OSA similar in male and female? This is an unresolved question since sex factors are overlooked in most clinical and experimental studies. Epidemiological data indicate that sex exerts an important influence in the prevalence of OSA and associated comorbidities, such as hypertension. Sex hormones, genetic and neural factors probably are the main players underlying sex differences in the pathophysiology of OSA but they are not yet fully understood. We are using chronic intermittent hypoxia (CIH) as an experimental model of intermittent hypoxia such as those observed in OSA patients to investigate the cardiovascular, sympathetic and respiratory responses in female rats. Our recent studies show that adult and juvenile female rats exposed to CIH develop hypertension similar to age-matched CIH-male rats. Although both males and females develop hypertension after CIH, the most remarkable finding was that CIH-female rats develop changes in the respiratory modulation of sympathetic activity different from those observed in CIH-male rats, characterizing sex differences in the respiratory-sympathetic coupling in response to CIH. Specifically, in CIH-female rats, sympathetic overactivity is linked to inspiration while in CIH-male rats it is linked to the late phase of expiration. In this review we discuss the pathophysiological consequences of CIH, focusing in adult and juvenile female rats and how changes in the respiratory-sympathetic coupling may play a key role in CIH-induced sympathetic overactivity and hypertension in both male and female rats.
阻塞性睡眠呼吸暂停（OSA）是一种复杂的疾病，患者会经历间歇性缺氧发作，且男女均可患病。OSA患者除了出现其他多种功能障碍外，还存在高血压和交感神经过度活跃的情况。因此，一个重要的问题依然存在：与OSA相关的自主神经功能障碍在男性和女性中是否相似？由于大多数临床和实验研究都忽略了性别因素，所以这仍是一个未解决的问题。流行病学数据表明，性别对OSA及其相关合并症（如高血压）的患病率有重要影响。性激素、遗传和神经因素可能是OSA病理生理学中性别差异的主要影响因素，但尚未完全明确。我们使用慢性间歇性缺氧（CIH）作为间歇性缺氧的实验模型，就像在OSA患者中观察到的那样，来研究雌性大鼠的心血管、交感神经和呼吸反应。我们最近的研究表明，成年和幼年雌性大鼠暴露于CIH后会出现与年龄匹配的CIH雄性大鼠相似的高血压。尽管雄性和雌性大鼠在CIH后都会出现高血压，但最显著的发现是，CIH雌性大鼠交感神经活动的呼吸调节变化与CIH雄性大鼠不同，这体现了对CIH反应中呼吸 - 交感神经耦合的性别差异。具体而言，在CIH雌性大鼠中，交感神经过度活跃与吸气有关，而在CIH雄性大鼠中则与呼气后期有关。在这篇综述中，我们讨论了CIH的病理生理后果，重点关注成年和幼年雌性大鼠，以及呼吸 - 交感神经耦合的变化如何在CIH诱导的雄性和雌性大鼠交感神经过度活跃和高血压中发挥关键作用。
