Carotid body hypersensitivity in intermittent hypoxia and obtructive sleep apnoea

Abstract

Carotid bodies are the principal sensory organs for detecting changes in arterial blood oxygen concentration, and the carotid body chemoreflex is a major regulator of the sympathetic tone, blood pressure and breathing. Intermittent hypoxia is a hallmark manifestation of obstructive sleep apnoea (OSA), which is a widespread respiratory disorder. In the first part of this review, we discuss the role of carotid bodies in heightened sympathetic tone and hypertension in rodents treated with intermittent hypoxia, and the underlying cellular, molecular and epigenetic mechanisms. We also present evidence for hitherto‐uncharacterized role of carotid body afferents in triggering cellular and molecular changes induced by intermittent hypoxia. In the second part of the review, we present evidence for a contribution of a hypersensitive carotid body to OSA and potential therapeutic intervention to mitigate OSA in a murine model. image

Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia

“…Rather, it is due to a plethora of factors that collectively alter presympathetic neuron activity and disrupt respiratory-sympathetic coupling. These factors include overexpression of HIF-1α ( Karlen-Amarante et al, 2023 ), sensitization of central ( Molkov et al, 2011 ) and peripheral chemoreceptors ( Prabhakar et al, 2005 , 2023 ), and dysregulation of astrocyte homeostatic control of blood pressure ( Marina et al, 2020 ). However, more studies are needed to elucidate the complex mechanisms underlying sympathetic overactivation caused by CIH ( Guyenet et al, 2020 ; Barnes et al, 2022 ).…”

Hypoxia sensing in the body: An update on the peripheral and central mechanisms

“…The mechanisms underlying the potentiation of CB chemosensitivity by CIH have yet to be elucidated completely. However, compelling evidence indicates that excessive ROS formation in the glomus cells is an important mechanism leading to CB hypersensitivity (Prabhakar et al., 2023 ). Generation of ROS induced by CIH also occurs in ventromedullary regions encompassing the sympathetic and respiratory core circuitries and central O 2 sensors (Nanduri et al., 2018 ), supporting the hypothesis that central alterations are also part of the complex mechanisms underpinning the cardiorespiratory dysfunctions in CIH/OSA.…”

Chronic intermittent hypoxia reveals role of the Postinspiratory Complex in the mediation of normal swallow production

“…It is characterized by frequent bouts of apnea during sleep caused by pharyngeal collapse, resulting in multiple bouts of hypoxia referred to as chronic intermittent hypoxia (CIH). CIH increases the gain of the carotid body response to hypoxia, which seems to be a major cause for the multiple comorbidities of OSA ( Iturriaga, 2023 ; Prabhakar et al, 2023 ). These OSA-related comorbidities ( Pack, 2023 ) include an increase in mortality ( Vgontzas et al, 2023 ) and cancer risk ( Sánchez-de-la-Torre et al, 2023 ), increased arousal and sleep fragmentation ( Horner, 2023 ), increased sympathetic drive leading to cardiovascular disease, metabolic syndromes such as obesity and diabetes ( Kurnool et al, 2023 ), renal disease, asthma ( Bonsignore et al, 2019 ), and decreased cognition ( Brockmann and Gozal, 2022 ).…”