Hydrogen sulfide as an O2 sensor: A critical analysis

Abstract

There is increasing interest in the physiological actions and therapeutic potential of the gasotransmitter hydrogen sulfide (H2S). In addition to exerting antihypertensive, anti-inflammatory, antioxidant, and pro-angiogenic effects, H2S has been suggested to play a central and ubiquitous role in O2 sensing. According to this concept, because H2S is metabolized by oxidation, its cellular concentration varies inversely with the ambient pO2 such that hypoxia causes a rise in intracellular [H2S]; this then acts to induce appropriate cellular responses. In particular, it has been proposed that H2S underpins O2 sensing in the carotid body, which triggers increases in ventilation in response to hypoxemia, and also in pulmonary arteries, which constrict in response to local alveolar hypoxia. This process, termed hypoxic pulmonary vasoconstriction (HPV), acts to divert blood to better-oxygenated regions of the lung, thereby maintaining the ventilation–perfusion ratio and minimizing hypoxia-induced falls in blood O2 saturation. In this chapter, we present a critical review of the evidence supporting and questioning this model in both HPV and the carotid body.