Contribution of the carotid body to the cardiorespiratory and autonomic alterations induced by chronic intermittent hypoxia

Obstructive sleep apnea (OSA) is a major health problem affecting a large adult population, which is associated with somnolence, sleep fragmentation, and cognitive dysfunction. However, it is also an independent risk factor for hypertension and arrhythmia. A growing body of evidence suggests that an abnormal heightened carotid body (CB) chemosensory discharge induced by CIH produces the activation of the central chemoreflex pathway, leading to sympathetic activation, respiratory-sympathetic coupling, enhanced hypoxic ventilatory response and neurogenic hypertension. Oxidative stress, pro-inflammatory molecules, endothelin-1, angiotensin-II, and reduced NO levels in the CB have been linked to the chemosensory potentiation. Additionally, the CIH-induced CB chemosensory potentiation led to neuronal al glial activation in the nucleus of the solitary tract (NTS). The autonomic and cardiorespiratory alterations induced by CIH depend on the CB integrity. Accordingly, CB ablation in rats performed at 21 days of CIH abolished the hypertension, the enhanced hypoxic ventilatory response and the oxidative stress in the NTS, even when rats were kept for one more week in CIH and the systemic oxidative stress persisted. Remarkably, the section of the carotid sinus nerves in mice performed at 50 days of CIH, not only normalized the elevated arterial blood pressure and the enhanced hypoxic ventilatory response but also reduced the increased levels of proinflammatory cytokines IL-6 and TNF-α and the microglia morphological changes in the NTS. Therefore, these results suggest that the CB plays a crucial role in the maintenance of hypertension and enhanced ventilatory responses induced by long-term CIH and contributes to the formation of a neuroinflammatory niche in the NTS by modifying microglial cell activity. These results support the proposal that removal of CB afferents may be useful for improving cardiovascular and endocrine dysfunction in human sympathetic-related diseases Accordingly, the idea that surgical CB removal may be a suitable method to treat pathological consequences of human sympathetic diseases receive attention. However, bilateral resection of the CB in humans’ results in a permanent elimination of the hypoxic ventilatory response in normocapnic conditions. Since the CB chemoreceptor contributes to the regulation of respiratory gases, several concerns have been raised regarding potential negative effects of bilateral CB ablation. For these reasons, novel treatments intended to normalize the enhanced CB chemoreflex are needed to alleviate the effects of CIH. In this communication, I will discuss the biological impact of CIH on the CB function and the effects on autonomic and cardiorespiratory regulation.

Supported by Fondecyt Grant 1211443.

This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.