Expressions of angiotensin and cytokine receptors in the paracrine signaling of the carotid body in hypoxia and sleep apnea

• Angiotensin and cytokine receptors expressed in the carotid body play roles in modulating carotid chemoreceptor activities.
• Elevated expressions of angiotensin receptors and local angiotensin-generating system in the carotid body (CB) in hypoxia.
• Carotid body inflammation involves elevated local expressions of pro-inflammatory cytokines and cytokine receptors in hypoxia.
• Upregulated angiotensin and cytokine pathways augment chemoreceptor activities and mediate CB inflammation in sleep apnea.

Arterial chemoreceptors in the carotid body are central to the chemical control of breathing in the chemotransduction of physiological stimuli in the arterial blood for eliciting the chemoreflex, which mediates the respiratory, cardiovascular and autonomic responses to hypoxia, hypercapnia and acidosis. Recent evidence suggests that signaling molecules locally produced in the carotid body, including angiotensin II and pro-inflammatory cytokines play an important role in the modulation of the activity of carotid chemoreceptors, via the angiotensin and cytokine receptors expressed in the chemosensitive cells in an autocrine–paracrine manner. The carotid chemoreceptor activity is augmented in subjects at high altitude and in patients with sleep-disordered breathing. Maladaptive responses of the paracrine signaling to hypoxia in the carotid body have been proposed to play a pathogenic role in sleep apnea. Specifically, recent findings show significant increases in expressions of angiotensin receptors and components of a local angiotensin-generating system in the carotid body in sustained or intermittent hypoxia, which augments the chemoreceptor activity and also mediates the inflammatory response of the carotid body to hypoxia. In addition, inflammation of the carotid body involves an increased local expression of cytokine receptors and pro-inflammatory cytokines in sustained or intermittent hypoxia. This review aims to summarize the evidence supporting that the upregulated expression of the angiotensin receptors and cytokine pathways in the carotid body leads to augmented activities of the carotid chemoreceptor in hypoxic conditions, which could play a role in the pathophysiology of sleep apnea.