title: Central hydrogen sulphide mediates ventilatory responses to hypercapnia in adult conscious rats.
abstract: OBJECTIVE
  Hydrogen sulphide (H2S) is endogenously produced and plays an important role as a modulator of neuronal functions; however, its modulatory role in the central CO2 chemoreception is unknown. The aim of the present study was to assess the role of endogenously produced H2S in the ventilatory response to hypercapnia in adult conscious rats.
  
  
  METHODS
  Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) inhibitors (aminooxyacetate: AOA and propargylglycine: PAG respectively) and a H2S donor (sodium sulphide: Na2S) were microinjected into the fourth ventricle (4V). Ventilation (V̇(E)), oxygen consumption (V̇O2) and body temperature were recorded before (room air) and during a 30-min CO2 exposure (hypercapnia, 7% CO2). Endogenous H2S levels were measured in the nucleus tractus solitarius (NTS).
  
  
  RESULTS
  Microinjection of Na2S (H2S donor), AOA (CBS inhibitor) or PAG (CSE inhibitor) did not affect baseline of the measured variables compared to control group (vehicle). In all experimental groups, hypercapnia elicited an increase in V̇(E). However, AOA microinjection, but not PAG, attenuated the ventilatory response to hypercapnia (P < 0.05), whereas Na2S elicited a slight, not significant, enhancement. Moreover, endogenous H2S levels were found higher in the NTS after hypercapnia (P < 0.05) compared to room air (normoxia) condition.
  
  
  CONCLUSIONS
  There are a few reports on the role of gaseous transmitters in the control of breathing. Importantly, the present data suggest that endogenous H2S via the CBS-H2S pathway mediates the ventilatory response to hypercapnia playing an excitatory role.
authors.affiliation: Dental School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: G S F
authors.initials: GS
authors.lastname: da Silva
authors.forename: R N
authors.initials: RN
authors.lastname: Soriano
authors.forename: M
authors.initials: M
authors.lastname: Kwiatkoski
authors.forename: H
authors.initials: H
authors.lastname: Giusti
authors.forename: M L
authors.initials: ML
authors.lastname: Glass
authors.forename: L G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000375:Aging / Q000378:metabolism; D000625:Aminooxyacetic Acid / Q000378:metabolism; D000818:Animals; D003541:Cystathionine beta-Synthase / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D004195:Disease Models, Animal; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D006935:Hypercapnia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology
chemical_list: D013440:Sulfides; D000625:Aminooxyacetic Acid; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: aminooxyacetate; central chemoreception; cystathionine beta-synthase; sodium sulphide; ventilation