Hydrogen sulfide attenuates hypoxia-induced respiratory suppression in anesthetized adult rats

• Hypoxia induced respiratory suppression and impaired some medullary neurons.
• Hypoxia increased the levels of some oxidative markers of medulla.
• Hypoxia decreased the levels of some anti-apoptotic markers of medulla.
• Hydrogen sulfide ameliorated the changes of all the parameters mentioned above.

Our previous study in vitro showed that hydrogen sulfide (H2S) could protect the medullary respiratory centers from injury induced by acute hypoxia in brainstem slices of neonatal rats. The present study was carried out to determine if H2S could exhibit similar protective effects in adult rats and to explore the underlying mechanisms of its protection. It was observed that hypoxia induced a diphasic respiratory response, an excitatory phase followed by an inhibitory one, as indicated by an increase followed by a decrease in frequency of rhythmic discharge of the diaphragm. Nissl staining revealed that some of the neurons in the medullary respiratory related nuclei were impaired in hypoxia rats. Hypoxia led to increases in the content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), as well as a decrease in the level of Bcl-2 mRNA of the medulla oblongata. Intracerebroventricular injection of 2.5 mM NaHS (a donor of H2S) or L-cysteine (L-Cys, a substrate for H2S) could prevent inhibitory respiratory effect occurred in the rats with hypoxia. Exogenous application of NaHS and L-Cys could also reduce the content of MDA and the activities of SOD and GSH-Px, and increase the level of Bcl-2 mRNA expression of medulla oblongata caused by hypoxia. These results indicate that H2S could protect the medullary respiratory centers against injury induced by acute hypoxia in adult rats partly due to its anti-oxidant and anti-apoptotic effects.