Role of hydrogen sulfide in ventilatory responses to hypercapnia in the medullary raphe of adult rats

Autor(es)

Jacob Sabino, Joao Paulo ^[1] ; de Castro Oliveira, Lucas Vaz ^[1] ; Soriano, Renato Nery ^[2] ; Kwiatkoski, Marcelo ^[3] ; Branco, Luiz G. S. ^[4] ; da Silva, Glauber S. F. ^[5]

Afiliação do(s) autor(es)

^[1] Univ Fed Piaui, Dept Biophys & Physiol, Grad Program Pharmaceut Sci, Teresina, PI - Brazil

^[2] Univ Fed Juiz de Fora, Dept Basic Life Sci, Div Physiol & Biophys, Governador Valadares, MG - Brazil

^[3] Univ Fed Mato Grosso do Sul, Tres Lagoas, MS - Brazil

^[4] Univ Sao Paulo, Dept Morphol Physiol & Basic Pathol, Dent Sch Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[5] Univ Minas Gerais, Inst Biol Sci Fed, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Physiology; v. 106, n. 9, p. 1992-2001, SEP 2021.
• Citações Web of Science: 1

Resumo

New Findings What is the central question of this study? There is evidence that H2S plays a role in the control of breathing: what are its actions on the ventilatory and thermoregulatory responses to hypercapnia via effects in the medullary raphe, a brainstem region that participates in the ventilatory adjustments to hypercapnia? What is the main finding and its importance? Hypercapnia increased the endogenous production of H2S in the medullary raphe. Inhibition of endogenous H2S attenuated the ventilatory response to hypercapnia in unanaesthetized rats, suggesting its excitatory action via the cystathionine beta-synthase-H2S pathway in the medullary raphe. Hydrogen sulfide (H2S) has been recently recognized as a gasotransmitter alongside carbon monoxide (CO) and nitric oxide (NO). H2S seems to modulate the ventilatory and thermoregulatory responses to hypoxia and hypercapnia. However, the action of the H2S in the medullary raphe (MR) on the ventilatory responses to hypercapnia remains to be elucidated. The present study aimed to assess the role of H2S in the MR (a brainstem region that contains CO2-sensitive cells and participates in the ventilatory adjustments to hypercapnia) in the ventilatory responses to hypercapnia in adult unanaesthetized Wistar rats. To do so, aminooxyacetic acid (AOA; a cystathionine beta-synthase (CBS) enzyme inhibitor), propargylglycine (PAG; a cystathionine gamma-lyase enzyme inhibitor) and sodium sulfide (Na2S; an H2S donor) were microinjected into the MR. Respiratory frequency (f(R)), tidal volume (V-T), ventilation (V?E), oxygen consumption (V?O2) and body temperature (T-b) were measured under normocapnic (room air) and hypercapnic (7% CO2) conditions. H2S concentration within the MR was determined. Microinjection of the drugs did not affect f(R), V-T and V?E during normocapnia when compared to the control group. However, the microinjection of AOA, but not PAG, attenuated f(R) and V?E during hypercapnia in comparison to the vehicle group, but had no effects on T-b. In addition, we observed an increase in the endogenous production of H2S in the MR during hypercapnia. Our findings indicate that endogenously produced H2S in the MR plays an excitatory role in the ventilatory response to hypercapnia, acting through the CBS-H2S pathway. (AU)

• Processo FAPESP: 15/24950-3 - Papel do sulfeto de hidrogênio (H2S) na resposta ventilatória à hipercapnia
• Beneficiário: Luiz Guilherme de Siqueira Branco
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/14779-4 - Efeito do sulfeto de hidrogênio (H2S) no NTS comissural sobre as respostas ventilatórias e hemodinâmicas à hipercapnia e hipóxia em animais hipertensos e normotensos
• Beneficiário: João Paulo Jacob Sabino
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/17681-9 - Alterações fisiopatológicas durante a inflamação sistêmica
• Beneficiário: Luiz Guilherme de Siqueira Branco
• Modalidade de apoio: Auxílio à Pesquisa - Temático