Hypoxia-induced arterial chemoreceptor stimulation and Hydrogen sulfide: Too much or too little?

This brief review presents and discusses some of the important issues surrounding the theory which asserts that endogenous hydrogen sulfide (H2S) is the mediator of, or at least an important contributor to, hypoxia-induced arterial chemorereceptor stimulation. The view presented here is that before H2S can seriously be considered as a candidate for transducing the O2-signal in the carotid bodies (CB), fundamental contradictions need to be resolved. One of these major contradictions is certainly the discrepancy between the levels of H2S endogenously present in the CB during hypoxia compared to the levels required to stimulate the arterial chemoreceptors in vitro. Very small amounts of H2S are thought to be produced endogenously during a given level of hypoxia, yet the partial pressure of tissue H2S which is needed to produce an effect commensurate with that of hypoxia is thousands to millions of times higher. This review discusses this and other contradictions in light of what is known about H2S concentration and production in various tissues, the lessons we have learnt from the response to exogenous sulfide and the ability of the blood and the mitochondria to oxidize very large amounts of sulfide. These considerations suggest that the increased production of H2S in hypoxia and exogenous sulfide cannot produce the same effect on the carotid bodies and breathing. While the effects of the endogenous H2S on breathing remains to be established, the effects exogenous sulfide can be accounted for by its long established toxicity on cytochrome C oxidase.

► Hydrogen sulfide has been proposed to transduce the effects of hypoxia in the carotid bodies. ► This review discusses the limits of this hypothesis. ► The effects of toxic/large doses of sulfide should not be confused with the putative role of endogenous H2S.