NO modulation of carotid body chemoreception in health and disease

Nitric oxide (NO), at physiological concentrations, is a tonic inhibitory modulator of carotid body (CB) chemosensory discharges. NO modulates the chemoreception process by several mechanisms, indirectly by modifying the vascular tone and oxygen delivery, and directly through the modulation of the excitability of glomus cells and petrosal neurons. In addition to the inhibitory effect, at high concentrations NO has a dual dose-dependent effect on CB chemoreception that depends on the P_O2${\text{P}}_{{\text{O}}_2}$. In hypoxic conditions, NO is primarily an inhibitory modulator of CB chemoreception, while in normoxia NO increases the chemosensory discharges. In this review, we will examine new evidence supporting the idea that NO is involved in the CB chemosensory potentiation induced by congestive heart failure (CHF) and chronic intermittent hypoxia (CIH), the main feature of obstructive sleep apnea (OSA). Evidence from patients and experimental animal models indicates that CHF and OSA, as well as CIH, potentiate the carotid hypoxic chemoreflexes, contributing to enhance the sympathetic tone. Moreover, animals exposed to CIH or to pacing-induced CHF showed enhanced baseline CB discharges in normoxia and potentiated chemosensory responses to acute hypoxia. Several molecules and pathways are altered in CHF, OSA and CIH, but the available evidence suggests that a reduced NO production in the CB plays an essential role in both diseases, contributing to enhance the CB chemosensory discharges.