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

Abstract

Endogenous H2S 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, H2S 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 H2S dissolved in the arterial blood able to stimulate the CB and to stop breathing in 8 spontaneously‐breathing anesthetized rats. H2S partial pressure (PaH2S) and gaseous concentrations were determined in the arterial blood from alveolar PH2S during continuous venous infusion of NaHS. This approach overcomes most of the issues of other techniques that directly measure H2S dissolved in the blood. A stimulation of breathing occurred for a PaH2S of 0.007±0.003 mmHg, corresponding to a concentration of gaseous and total dissolved H2S of at most 0.63±0.31 μM and 1.89±0.93 μM. A rapid reduction in breathing occurred at a PaH2S of 0.042±0.020 mmHg, gaseous H2S of 3.68±1.72 μM, and total dissolved H2S of 11.04±5.16 μM. H2S affects the CB and RN in‐vivo via mechanisms independent of CCO. Whether these low levels of dissolved H2S are low enough to be compatible with the levels of H2S endogenously produced remains to be determined. Support provided by NIH grant 1R21NS080788–01.