Laboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Curr Hypertens Rep. 2019 Oct 10;21(11):89. doi: 10.1007/s11906-019-0995-y.
Obstructive sleep apnea (OSA), featured by chronic intermittent hypoxia (CIH), is an independent risk for systemic hypertension (HTN) and is associated with pulmonary hypertension (PH). The precise mechanisms underlying pulmonary vascular remodeling and PH in OSA are not fully understood. However, it has been suggested that lung tissue hypoxia, oxidative stress, and pro-inflammatory mediators following CIH exposure may contribute to PH.
New evidences obtained in preclinical OSA models support that an enhanced carotid body (CB) chemosensory reactiveness to oxygen elicits sympathetic and renin-angiotensin system (RAS) overflow, which contributes to HTN. Moreover, the ablation of the CBs abolished the sympathetic hyperactivity and HTN in rodents exposed to CIH. Accordingly, it is plausible that the enhanced CB chemosensory reactivity may contribute to the pulmonary vascular remodeling and PH through the overactivation of the sympathetic-RAS axis. This hypothesis is supported by the facts that (i) CB stimulation increases pulmonary arterial pressure, (ii) denervation of sympathetic fibers in pulmonary arteries reduces pulmonary remodeling and pulmonary arterial hypertension (PAH) in humans, and (iii) administration of angiotensin-converting enzyme (ACE) or blockers of Ang II type 1 receptor (ATR1) ameliorates pulmonary remodeling and PH in animal models. In this review, we will discuss the supporting evidence for a plausible contribution of the CB-induced sympathetic-RAS axis overflow on pulmonary vascular remodeling and PH induced by CIH, the main characteristic of OSA.
阻塞性睡眠呼吸暂停（OSA）以慢性间歇性低氧（CIH）为特征，是全身性高血压（HTN）的独立危险因素，并与肺动脉高压（PH）相关。OSA 中肺血管重塑和 PH 的精确机制尚不完全清楚。然而，据推测，CIH 暴露后肺组织缺氧、氧化应激和促炎介质可能导致 PH。
在临床前 OSA 模型中获得的新证据支持颈动脉体（CB）对氧的化学感受器反应增强引发交感神经和肾素-血管紧张素系统（RAS）溢出，从而导致 HTN。此外，在暴露于 CIH 的啮齿动物中，CB 的消融消除了交感神经亢进和 HTN。因此，增强的 CB 化学感受器反应可能通过过度激活交感神经-RAS 轴导致肺血管重塑和 PH，这一假设是合理的。这一假设得到了以下事实的支持：（i）CB 刺激增加肺动脉压，（ii）肺动脉交感神经纤维去神经支配可减少人类的肺重塑和肺动脉高压（PAH），以及（iii）血管紧张素转换酶（ACE）或血管紧张素 II 型 1 受体（ATR1）阻滞剂的给药可改善动物模型中的肺重塑和 PH。在这篇综述中，我们将讨论支持 CB 诱导的交感神经-RAS 轴溢出对 CIH 诱导的肺血管重塑和 PH 的假设的证据，这是 OSA 的主要特征。
