Endogenous hydrogen sulfide maintains eupnea in an in situ arterially perfused preparation of rats

Abstract

Hydrogen sulfide (H2S) is constitutively generated in the human body and works as a gasotransmitter in synaptic transmission. In this study, we aimed to evaluate the roles of endogenous H2S in generating eupnea at the respiratory center. We employed an in situ arterially perfused preparation of decerebrated rats and recorded the central respiratory outputs. When the H2S-producing enzyme cystathionine β-synthase (CBS) was inhibited, respiration switched from the 3-phase eupneic pattern, which consists of inspiration, postinspiration, and expiration, to gasping-like respiration, which consists of inspiration only. On the other hand, when H2S synthesis was inhibited via cystathionine γ-lyase (CSE) or when H2S synthesis was activated via CBS, eupnea remained unchanged. These results suggest that H2S produced by CBS has crucial roles in maintaining the neuronal network to generate eupnea. The mechanism of respiratory pattern generation might be switched from a network-based system to a pacemaker cell-based system in low H2S conditions.

Hydrogen sulfide production in the medullary respiratory center modulates the neural circuit for respiratory pattern and rhythm generations

“…Although HA can also inhibit cystathionine γ-lyase (CSE), the other H 2 S synthase, it does not affect our conclusion because CSE is mainly expressed in peripheral tissue and less in the central nervous system 1 , 46 . Additionally, a previous study showed that a CSE-selective inhibitor does not affect the respiratory pattern 7 . Therefore, it seems that the effects of HA microinjection into the medullary respiratory network in this study caused the reduction in H 2 S synthesis mediated by inhibition of CBS, not of CSE.…”

“…The BötC is a region for generation of the expiratory phase with abundant expiratory neurons, and this region's excitation prolongs expiratory phase duration 27 , 28 . H 2 S production modulates synaptic transmission, and it was previously reported that it can regulate neural networks to maintain respiration 7 . Moreover, it has been reported that the sparse neural network at the respiratory network increases respiratory frequency and decreases the inspiratory burst 29 .…”

“…Experiments were performed on 90 male Wistar rats (aged 3–4 weeks; Japan SLC, Inc.) using an in situ arterially perfused preparation. The general methods were based on those of previous studies 7 , 15 .…”

“…Some studies have suggested that H 2 S is involved in respiratory central pattern generation in the brainstem. Manipulation of H 2 S synthesis modified the respiratory frequency, inspiratory burst power, and respiratory pattern in in vitro experiments on medullary slices, in vivo experiments on anesthetized rats, and an in situ arterially perfused preparation 3 , 7 , 8 . H 2 S is also involved in ventilatory responses under hypoxia/hypercapnia conditions 8 – 10 .…”