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 (HS). In addition to exerting antihypertensive, anti-inflammatory, antioxidant, and pro-angiogenic effects, HS has been suggested to play a central and ubiquitous role in O sensing. According to this concept, because HS is metabolized by oxidation, its cellular concentration varies inversely with the ambient pO such that hypoxia causes a rise in intracellular [HS]; this then acts to induce appropriate cellular responses. In particular, it has been proposed that HS underpins O 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 O saturation. In this chapter, we present a critical review of the evidence supporting and questioning this model in both HPV and the carotid body.

Protective effect of hydrogen sulfide on the kidney (Review)

“…H 2 S-mediated O 2 sensing has been detected in various O 2 -sensing tissues in the cardiovascular and respiratory systems of vertebrates ( 35 , 36 ). The effect of H 2 S on downstream signaling events is consistent with that of hypoxia activation ( 37 , 38 ).…”

Hypoxia releases S-nitrosocysteine from carotid body glomus cells—relevance to expression of the hypoxic ventilatory response

“…At the peripheral level, the carotid body contains, numerous excitatory and inhibitory neurotransmitters released by primary glomus cells (PGCs) in response to changes in ventilation ( Prabhakar, 1994 ; Iturriaga and Alcayaga, 2004 ; Rey and Iturriaga, 2004 ; Bairam and Carroll, 2005 ; Kumar, 2007 ; Shirahata et al, 2007 ; Iturriaga et al, 2009 ; Nurse and Piskuric, 2013 ; Nurse, 2014 ; Gonkowski, 2020 ; Bardsley et al, 2021 ; Gold et al, 2022 ). However, there is no current agreement as to the identity of the primary neurotransmitter released by PGCs to drive the hypoxic ventilatory response ( Eyzaguirre and Fidone, 1980 ; Iturriaga and Alcayaga, 2004 ; Nurse, 2005 ; Lahiri et al, 2006 ; Iturriaga et al, 2009 ; Gonzalez et al, 2010 ; Prieto-Lloret and Aaronson, 2017 ; Aldossary et al, 2020 ; Gold et al, 2022 ).…”