title: Endogenous hydrogen sulfide in the rostral ventrolateral medulla/Bötzinger complex downregulates ventilatory responses to hypoxia.
abstract: Hydrogen sulfide (H2S) is now recognized as a new gaseous transmitter involved in several brain-mediated responses. The rostral ventrolateral medulla (RVLM)/Bötzinger complex is a region in the brainstem that is involved in cardiovascular and respiratory functions. Recently, it has been shown that exogenous H2S in the RVLM modulates autonomic function and thus blood pressure. In the present study, we investigated whether H2S, endogenously produced in the RVLM/Bötzinger complex, plays a role in the control of hypoxia-induced hyperventilation. Ventilation (VE) was measured before and after bilateral microinjection of Na2S (H2S donor, 0.04, 1 and 2 pmol/100 nl) or aminooxyacetate (AOA, 0.2, 1 and 2 pmol/100 nl, a cystathionine β-synthase, CBS, inhibitor) into the RVLM/Bötzinger complex followed by a 60-min period of hypoxia (7% inspired O2) or normoxia exposure. Control rats received microinjection of vehicle. Microinjection of vehicle, AOA or Na2S did not change VE in normoxic conditions. Exposure to hypoxia evoked a typical increase in VE. Microinjection of Na2S (2 pmol) followed by hypoxia exposure attenuated the hyperventilation. Conversely, microinjection of AOA (2 pmol) into the RVLM/Bötzinger complex caused an increase in the hypoxia-induced hyperventilation. Thus, endogenous H2S in the RVLM/Bötzinger complex seems to play no role in the maintenance of basal pulmonary ventilation during normoxia whereas during hypoxia H2S has a downmodulatory function. Homogenates of RVLM/Bötzinger complex of animals previously exposed to hypoxia for 60 min exhibited a decreased rate of H2S production. Our data are consistent with the notion that the gaseous messenger H2S synthesis is downregulated in the RVLM/Bötzinger complex during hypoxia favoring hyperventilation.
authors: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, SP, Brazil.
authors: Alberto F
authors: AF
authors: Donatti
authors: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, SP, Brazil.
authors: Renato N
authors: RN
authors: Soriano
authors: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, SP, Brazil.
authors: João P
authors: JP
authors: Sabino
authors: Department of Morphology, Physiology and Basic Pathology, Dental School of Ribeirão Preto, University of São Paulo, 14040-904 Ribeirão Preto, SP, Brazil. Electronic address: branco@forp.usp.br.
authors: Luiz G S
authors: LG
authors: Branco
mesh_terms: D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D002408:Catheters, Indwelling; D002491:Central Nervous System Agents / Q000494:pharmacology; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D006985:Hyperventilation / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology*; D008845:Microinjections; D010991:Plethysmography; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology
chemical_list: D002491:Central Nervous System Agents; D004791:Enzyme Inhibitors; D013431:Sulfates; C012036:sodium sulfate; D000625:Aminooxyacetic Acid; D003541:Cystathionine beta-Synthase; D006862:Hydrogen Sulfide
keywords: Aminooxyacetate; Central nervous system; Cystathionine beta-synthase; Hyperpnea; Sodium sulfide; Ventilation