title: Endogenous preoptic hydrogen sulphide attenuates hypoxia-induced hyperventilation.
abstract: OBJECTIVE
  We hypothesized that hydrogen sulphide (H2 S), acting specifically in the anteroventral preoptic region (AVPO - an important integrating site of thermal and cardiorespiratory responses to hypoxia in which H2 S synthesis has been shown to be increased under hypoxic conditions), modulates the hypoxic ventilatory response.
  
  
  METHODS
  To test this hypothesis, we measured pulmonary ventilation (V˙E) and deep body temperature of rats before and after intracerebroventricular (icv) or intra-AVPO microinjection of aminooxyacetate (AOA; CBS inhibitor) or Na2 S (H2 S donor) followed by 60 min of hypoxia exposure (7% O2 ). Furthermore, we assessed the AVPO levels of H2 S of rats exposed to hypoxia. Control rats were kept under normoxia.
  
  
  RESULTS
  Microinjection of vehicle, AOA or Na2 S did not change V˙E under normoxic conditions. Hypoxia caused an increase in ventilation, which was potentiated by microinjection of AOA because of a further augmented tidal volume. Conversely, treatment with Na2 S significantly attenuated this response. The in vivo H2 S data indicated that during hypoxia the lower the deep body temperature the smaller the degree of hyperventilation. Under hypoxia, H2 S production was found to be increased in the AVPO, indicating that its production is responsive to hypoxia. The CBS inhibitor attenuated the hypoxia-induced increase in the H2 S synthesis, suggesting an endogenous synthesis of the gas.
  
  
  CONCLUSIONS
  These data provide solid evidence that AVPO H2 S production is stimulated by hypoxia, and this gaseous messenger exerts an inhibitory modulation of the hypoxic ventilatory response. It is probable that the H2 S modulation of hypoxia-induced hyperventilation is at least in part in proportion to metabolism.
authors.affiliation: Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Kwiatkoski
authors.forename: R N
authors.initials: RN
authors.lastname: Soriano
authors.forename: G S F
authors.initials: GS
authors.lastname: da Silva
authors.forename: H D
authors.initials: HD
authors.lastname: Francescato
authors.forename: T M
authors.initials: TM
authors.lastname: Coimbra
authors.forename: M L
authors.initials: ML
authors.lastname: Glass
authors.forename: E C
authors.initials: EC
authors.lastname: Carnio
authors.forename: L G S
authors.initials: LG
authors.lastname: Branco
mesh_terms: D000625:Aminooxyacetic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D006862:Hydrogen Sulfide / Q000008:administration & dosage / Q000494:pharmacology*; D006985:Hyperventilation / Q000378:metabolism*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D011301:Preoptic Area; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000625:Aminooxyacetic Acid; D006862:Hydrogen Sulfide
keywords: aminooxyacetate; cystathionine beta-synthase; hyperpnea; hypothalamus; sodium sulphide; ventilation