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. 0.4μmol (concentration: 800μM), was needed to stimulate breathing within 1s following i.v. injection. Above this level (and up to 2.4μmol, with a concentration of 4800μM), 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 PaO2 between 23 and >760mmHg. 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.
All Science Journal Classification (ASJC) codes
- Pulmonary and Respiratory Medicine