H₂S mediates O₂ sensing in the carotid body

Gaseous messengers, nitric oxide and carbon monoxide, have been implicated in O₂ sensing by the carotid body, a sensory organ that monitors arterial blood O₂ levels and stimulates breathing in response to hypoxia. We now show that hydrogen sulfide (H₂S) is a physiologic gasotransmitter of the carotid body, enhancing its sensory response to hypoxia. Glomus cells, the site of O₂ sensing in the carotid body, express cystathionine γ-lyase (CSE), an H₂S-generating enzyme, with hypoxia increasing H₂S generation in a stimulus-dependent manner. Mice with genetic deletion of CSE display severely impaired carotid body response and ventilatory stimulation to hypoxia, as well as a loss of hypoxia-evoked H₂S generation. Pharmacologic inhibition of CSE elicits a similar phenotype in mice and rats. Hypoxia-evoked H₂S generation in the carotid body seems to require interaction of CSE with hemeoxygenase-2, which generates carbon monoxide. CSE is also expressed in neonatal adrenal medullary chromaffin cells of rats and mice whose hypoxia-evoked catecholamine secretion is greatly attenuated by CSE inhibitors and in CSE knockout mice.