Carotid Body contribution to the physio-pathological consequences of intermittent hypoxia: Role of nitro-oxidative stress and inflammation.

Obstructive sleep apnoea (OSA) characterised by chronic intermittent hypoxia (CIH) is considered as an independent risk for hypertension. Pathological cardiorespiratory consequences of OSA have been attributed to systemic oxidative stress, inflammation, and sympathetic overflow induced by CIH, but an emerging body of evidence indicates that a nitro-oxidative and pro-inflammatory milieu within the carotid body (CB) is involved in the potentiation of CB chemosensory responses to hypoxia, which contribute to enhance the sympathetic activity. Accordingly, autonomic and cardiovascular alterations induced by CIH are critically dependent on an abnormal heightened CB chemosensory input to the nucleus of tractus solitarius (NTS), where second order neurons projects to the rostral ventrolateral medulla (RVLM), activating pre-sympathetic neurons that control pre-ganglionic sympathetic neurons. CIH produces oxidative stress and neuroinflammation in the NTS and RVLM, which may contribute to the long-term irreversibility of the CIH-induced alterations. This brief review is mainly focused on the contribution of nitro-oxidative stress and pro-inflammatory molecules on the hyperactivation of the hypoxic chemoreflex pathway including the CB and the brainstem centres, and whether the persistence of autonomic and cardiorespiratory alterations may depend on the glial-related neuroinflammation induced by the enhanced CB chemosensory afferent input. Abstract figure legend Proposed role for the carotid body (CB)-mediated enhanced cardiorespiratory reflex following intermittent hypoxia, the main feature of obstructive sleep apnoea. The oxidative stress and a pro-inflammatory milieu within the CB are associated with an enhanced chemosensory input that potentiate the central CB chemoreflex pathway, leading to autonomic and cardiorespiratory alterations including hypertension. In the brainstem cardiorespiratory centres, the hyperactivation of the neurons contributes to the glial (microglia and/or astrocyte) activation increasing local levels of ROS, pro-inflammatory cytokines, and Ang II. This article is protected by copyright. All rights reserved.