Potential Contribution of Carotid Body-Induced Sympathetic and Renin-Angiotensin System Overflow to Pulmonary Hypertension in Intermittent Hypoxia.

PURPOSE OF REVIEW

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.

RECENT FINDINGS

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.