Inhibitory effects of hyperoxia and methemoglobinemia on H2S induced ventilatory stimulation in the rat

The aim of this study was to clarify, using in vitro and in vivo approaches in the rat, the site of mediation of the inhibition of H2S induced arterial chemoreceptor stimulation, by hyperoxia and methemoglobinemia. We first determined the ventilatory dose–response curves during intravenous injections of H2S. A very high dose of NaHS, i.e. 0.4 μmol (concentration: 800 μM), was needed to stimulate breathing within 1 s following i.v. injection. Above this level (and up to 2.4 μmol, with a concentration of 4800 μM), a dose-dependent effect of H2S injection was observed. NaHS injection into the thoracic aorta produced the same effect, suggesting that within one circulatory time, H2S pulmonary exchange does not dramatically reduce H2S concentrations in the arterial blood. The ventilatory response to H2S was abolished in the presence of MetHb (12.8%) and was significantly depressed in hyperoxia and, surprisingly, in 10% hypoxia. MetHb per se did not affect the ventilatory response to hypoxia or hyperoxia, but dramatically enhanced the oxidation of H2S in vitro, with very fast kinetics. These findings suggest that, the decrease/oxidation of exogenous H2S in the blood is the primary effect of MetHb in vivo. In contrast, the in vitro oxidative properties of blood for H2S were not affected by the level of PaO2PaO2 between 23 and >760 mmHg. This suggests that the inhibition of the ventilatory response to H2S by hyperoxia during aortic or venous injection originates within the CB and not in the blood. The implications of these results on the role of endogenous H2S in the arterial chemoreflex are discussed.

► Millimolar concentrations of H2S are needed to stimulate breathing in the rat following intravenous or intra-aortic injections.
► Hyperoxia and the presence of methemoglobin abolish H2S induced ventilatory stimulation.
► High PaO2PaO2 interacts with H2S at the carotid body level while methemoglobinemia increases sulfide oxidation in the blood.