Very low levels of H2S in the blood are needed to affect the medullary respiratory neurons and the arterial chemoreceptors in‐vivo

Endogenous H 2 S has been proposed to be involved in the generation of breathing by the brainstem respiratory neurons (RN) and to transduce the effects of hypoxemia in the arterial chemoreceptors (CB). However, H 2 S at concentrations which should inhibit the cytochrome C oxidase (CCO) activity, i.e. above 30 μM, have been used in‐vitro to stimulate the CB (30–100 μM) or to affect the RN (200 μM). We determined the concentration of H 2 S dissolved in the arterial blood able to stimulate the CB and to stop breathing in 8 spontaneously‐breathing anesthetized rats. H 2 S partial pressure (PaH 2 S) and gaseous concentrations were determined in the arterial blood from alveolar PH 2 S during continuous venous infusion of NaHS. This approach overcomes most of the issues of other techniques that directly measure H 2 S dissolved in the blood. A stimulation of breathing occurred for a PaH 2 S of 0.007±0.003 mmHg, corresponding to a concentration of gaseous and total dissolved H 2 S of at most 0.63±0.31 μM and 1.89±0.93 μM. A rapid reduction in breathing occurred at a PaH 2 S of 0.042±0.020 mmHg, gaseous H 2 S of 3.68±1.72 μM, and total dissolved H 2 S of 11.04±5.16 μM. H 2 S affects the CB and RN in‐vivo via mechanisms independent of CCO. Whether these low levels of dissolved H 2 S are low enough to be compatible with the levels of H 2 S endogenously produced remains to be determined. Support provided by NIH grant 1R21NS080788–01 .