Complementary roles of gasotransmitters CO and H₂S in sleep apnea

Significance The carotid body (CB) is the major sensory organ responsible for monitoring arterial blood oxygen content. Glomus cells in the CB express heme oxygenase 2 (HO-2) and cystathionine-γ-lyase (CSE), enzymes that generate the gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H 2 S), respectively. In normoxia, CO inhibits CSE from producing H 2 S. During hypoxia, HO-2 produces less CO, resulting in increased H 2 S production, which stimulates CB activity, leading to increases in respiratory rate, heart rate, and blood pressure. We report that decreased CO and increased H 2 S generation in the CB causes sleep apnea in HO-2 knockout mice and spontaneously hypertensive rats. An inhibitor of CSE eliminates sleep apnea when administered to these animals, suggesting that this approach may have therapeutic utility in patients with sleep apnea.