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

Minako Okazaki,Masayuki Matsumoto,Tadachika Koganezawa,Saori Uozu,Yuma Sato

doi:10.1038/s42003-020-01312-6

Minako Okazaki, Masayuki Matsumoto + Show 3 more

Open Access

https://doi.org/10.1038/s42003-020-01312-6

Copy DOI

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.

Highlights

Hydrogen sulfide (H2S) is constitutively generated in the human body and works as a gasotransmitter in synaptic transmission
To confirm the functional roles of H2S production via CBS in respiratory pattern generation, we observed the effects of administration of the CBS inhibitors AOA (Fig. 1a) and HA (Fig. 1b) in the in situ arterially perfused preparation
The phrenic and vagus nerve activities had the rhythmic three-phase respiratory pattern, which consists of incremental activity of the phrenic and vagus nerves in the inspiratory phase, short excitation of the vagus nerve in the postinspiratory phase, and slow decrement of the vagus nerve activity in the expiratory phase (i in Fig. 1c, d)

Summary

Introduction

Hydrogen sulfide (H2S) is constitutively generated in the human body and works as a gasotransmitter in synaptic transmission. Hydrogen sulfide has been referred to as the third gaseous signaling molecule, after carbon monoxide (CO) and nitric oxide (NO) It is involved in several brain-mediated responses and regulates many body functions by changing the transmission efficiency between presynapse and postsynapse depending on the physiological conditions[6,7]. Application of an H2S donor or inhibition of H2S synthesis in the respiratory center changes the burst frequency or ventilatory outputs as shown in slice preparations or rhythmic brainstem spinal cord preparation of neonatal rats and in vivo preparation of adult rats[13,14,15] This suggests that endogenous H2S may affect respiratory pattern generation in the brain. This finding indicates that the respiratory pattern-generating mechanism is maintained by H2S in eupnea

Objectives

Methods

Results

Conclusion