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 (H(2)S) is the mediator of, or at least an important contributor to, hypoxia-induced arterial chemorereceptor stimulation. The view presented here is that before H(2)S can seriously be considered as a candidate for transducing the O(2)-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 H(2)S endogenously present in the CB during hypoxia compared to the levels required to stimulate the arterial chemoreceptors in vitro. Very small amounts of H(2)S are thought to be produced endogenously during a given level of hypoxia, yet the partial pressure of tissue H(2)S 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 H(2)S 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 H(2)S in hypoxia and exogenous sulfide cannot produce the same effect on the carotid bodies and breathing. While the effects of the endogenous H(2)S on breathing remains to be established, the effects exogenous sulfide can be accounted for by its long established toxicity on cytochrome C oxidase.