Hydrogen Sulfide and Oxygen Sensing in the Cardiovascular System

Vertebrate cardiorespiratory homeostasis is inextricably dependent upon specialized cells that provide feedback on oxygen status in the tissues, blood, and on occasion, environment. These oxygen sensing cells include chemoreceptors and oxygen-sensitive chromaffin cells that initiate cardiorespiratory reflexes, vascular smooth muscle cells that adjust perfusion to metabolism or ventilation, and other cells that condition themselves in response to episodic hypoxia. Identification of how these cells sense oxygen and transduce this into the appropriate physiological response has enormous clinical applicability, but despite intense research there is no consensus regarding the initial hypoxia-effector coupling mechanism. This review examines an alternative mechanism of oxygen sensing using oxidation of endogenously produced hydrogen sulfide (H2S) as the O-2-sensitive couple. Support for this hypothesis includes the similarity of effects of hypoxia and H2S on a variety of tissues, augmentation of hypoxic responses by precursors of H2S production and their inhibition by inhibitors of H2S synthesis, and the rapid consumption of H2S by O-2 in the range of intracellular/mitochondrial Po-2. These studies also indicate that, under normoxic conditions, it is doubtful that free H2S has longer than a transient existence in tissue or extracellular fluid. Antioxid. Redox Signal. 12, 1219-1234.